Aging - Envejecimiento

TÍTULO / TITLE: - Down Syndrome and Alzheimers Disease: A Qualitative Study Exploring Understanding and Perceptions of Dementia and Diagnostic Pathways Among People With Down Syndrome and Their Families

REVISTA / JOURNAL: - J Intellect Disabil Res. 2026 Sep 11. doi: 10.1111/jir.70173. Online ahead of print.

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AUTORES / AUTHORS: - M L Healy et al.

INSTITUCIÓN / INSTITUTION: - Monash University, Melbourne, Victoria, Australia

RESUMEN / SUMMARY: - Background: People with Down syndrome are at high risk of Alzheimers disease. Dementia diagnosis and support are a growing challenge for health and social care systems. There is limited knowledge of the perceptions of dementia and dementia diagnostic pathways among people with Down syndrome and their families. Methods: A qualitative study was conducted with individuals with Down syndrome and their families to explore knowledge around dementia and perceptions of dementia diagnostic pathways. Applied thematic analysis was conducted with inductive and deductive coding. Results: Results showed that people with Down syndrome understood the concept of dementia. Families were aware of the association between Down syndrome and Alzheimers disease, but some were reluctant to discuss this with their family member. Families lacked confidence in current dementia diagnostic pathways and worried about the future. Conclusions: As people with Down syndrome age, improved dementia awareness, medical and social care supports and tailored service design will be critical.

TÍTULO / TITLE: - Imaging and plasma biomarkers for pathological accumulation in Down syndrome

REVISTA / JOURNAL: - Brain. 2026 Jun 3;149(6):1944-1957. doi: 10.1093/brain/awaf418. Free PMC article.

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AUTORES / AUTHORS: - Julie K Wisch et al

INSTITUCIÓN / INSTITUTION: - Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, USA.

RESUMEN / SUMMARY: - Down syndrome is characterized by triplication of chromosome 21, leading to early-onset Alzheimers disease pathology, with nearly all individuals with Down syndrome developing amyloid and tau pathology. In the new era of amyloid-modifying therapies, it is vital to identify early biomarkers for Alzheimers disease pathology in Down syndrome. Striatal amyloid may begin to accumulate sooner than cortical amyloid in Down syndrome. Tau phosphorylation at specific sites, including 217, can be quantified in plasma and may represent an important mechanistic step in the development of tau pathology. This study had two aims: (i) to compare the relative age at increase of multiple biomarkers (cortical amyloid, striatal amyloid, plasma pTau217 and summary tau pathology); and (ii) to test whether plasma pTau217 can identify both the current presence and likely future accumulation of amyloid and tau pathology. To identify optimal biomarkers for early intervention, we examined longitudinal cortical and striatal amyloid PET, plasma pTau217 and tau PET in 328 individuals with Down syndrome enrolled in the Alzheimer Biomarker Consortium-Down Syndrome study. To compare the timing of biomarker changes, we modelled longitudinal biomarkers using generalized additive mixed models relative to age. We used receiver operating characteristic curve analysis to identify thresholds for both current and likely future accumulation of amyloid and tau pathology. For all comparisons, we used age as the null model, performing DeLongs tests to evaluate the performance of age relative to biomarker-based prediction. Imaging biomarkers increased at around 40 years old, with plasma pTau217 increasing somewhat later than the three PET biomarkers. Striatal amyloid increased before cortical amyloid in some participants; however, this was not uniform across individuals. If an individual was classified as a reliable accumulator with one biomarker, he or she was likely to be a reliable accumulator in other biomar

TÍTULO / TITLE: - Dementia in Downs syndrome

REVISTA / JOURNAL: - Lancet Neurol. 2016 May;15(6):622-36. doi: 10.1016/S1474-4422(16)00063-6. Epub 2016 Apr 11.

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AUTORES / AUTHORS: - Clive Ballard et al.

INSTITUCIÓN / INSTITUTION: - Wolfson Centre for Age-Related Diseases, Kings College London, London, UK.

RESUMEN / SUMMARY: - Downs syndrome is the most common genetic cause of learning difficulties, and individuals with this condition represent the largest group of people with dementia under the age of 50 years. Genetic drivers result in a high frequency of Alzheimers pathology in these individuals, evident from neuroimaging, biomarker, and neuropathological findings, and a high incidence of cognitive decline and dementia. However, cognitive assessment is challenging, and diagnostic methods have not been fully validated for use in these patients; hence, early diagnosis remains difficult. Evidence regarding the benefits of cholinesterase inhibitors and other therapeutic options to treat or delay progressive cognitive decline or dementia is very scarce. Despite close similarities with late-onset Alzheimers disease, individuals with Downs syndrome respond differently to treatment, and a targeted approach to drug development is thus necessary. Genetic and preclinical studies offer opportunities for treatment development, and potential therapies have been identified using these approaches.

TÍTULO / TITLE: - Brain volume trajectories in Down syndrome and autosomal dominant Alzheimers disease

REVISTA / JOURNAL: - Alzheimers Dement. 2026 Jan;22(1):e71103. doi: 10.1002/alz.71103. Free PMC article.

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AUTORES / AUTHORS: - James T Kennedy et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.

RESUMEN / SUMMARY: - Introduction: It is unknown if neurodegeneration trajectories differ between Down syndrome (DS) and autosomal dominant Alzheimers disease (ADAD), both of which are genetic forms of Alzheimers disease (AD). Methods: We compared brain volumes in DS, ADAD, and unaffected family members serving as controls. Participants underwent magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET), deriving volumetric and amyloid burden, respectively. Nonlinear associations between regional volumes and estimated years to clinical symptom onset (EYO) were evaluated using generalized additive mixed-models. Results: Longitudinal data from 267 controls, 341 participants with DS, and 358 participants with ADAD were included, totaling 1908 scans. DS volumes were lower than ADAD and controls initially and dropped linearly. ADAD had similar volumes to controls until diverging, beginning at EYO -7. Amyloid was negatively associated with volume, with similar slopes in DS and ADAD. Discussion: ADAD and DS demonstrate distinct patterns of brain volume decline prior to symptom onset despite being similarly affected by amyloid.

TÍTULO / TITLE: - Peak width of skeletonized mean diffusivity reveals early and multifactorial white matter injury across sporadic and Down syndrome-associated Alzheimers disease

REVISTA / JOURNAL: - Alzheimers Dement. 2026 May;22(5):e71507. doi: 10.1002/alz.71507. Free PMC article.

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AUTORES / AUTHORS: - Alejandra O Morcillo-Nieto et al.

INSTITUCIÓN / INSTITUTION: - Sant Pau Memory Unit, IR SANT PAU, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

RESUMEN / SUMMARY: - Introduction: This study investigates the evolution with disease progression and pathological correlates of peak width of skeletonized mean diffusivity (PSMD), a sensitive diffusion magnetic resonance imaging (MRI) marker of microvascular white matter (WM) injury, in sporadic Alzheimers disease (sAD) and Down syndrome (DS)-associated AD (DSAD). Method: This cross-sectional study included 150 euploid controls, 118 subjects with sAD, and 228 DS adults (34.65% with symptomatic AD). PSMD was derived from 3T-MRI diffusion tensor imaging. Associations with sociodemographic, clinical stage, cerebrospinal fluid (CSF), and small vessel disease markers were examined. Results: PSMD correlated with age in all groups, showing a stronger association in DS, with alterations apparent 15 years before the populations dementia age at onset. In euploid and DS, higher PSMD correlated with AD severity, CSF-neurofilament light chain (NfL), microbleeds, and WM hyperintensities (WMH). PSMD abnormalities were more frequent than WMH, especially in DS. Discussion: PSMD is a sensitive early biomarker of WM injury across sAD and DSAD, preceding symptom onset and capturing multifactorial disease processes.

TÍTULO / TITLE: - Precision medicine for Alzheimers disease in Down syndrome

REVISTA / JOURNAL: - Alzheimers Dement. 2026 Apr;22(4):e71398. doi: 10.1002/alz.71398. Free PMC article.

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AUTORES / AUTHORS: - Sonal Sukreet et al.

INSTITUCIÓN / INSTITUTION: - Departments of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, San Diego, California, USA.

RESUMEN / SUMMARY: - Introduction: Down syndrome (DS) exhibits a genetic form of Alzheimers disease (AD). We used a blood-based proteomic algorithm to predict cognitive status, treatment responders, and change to vitamin E in DS adults from a completed clinical trial, "Vitamin E in Aged Persons with Down Syndrome," which originally showed no significant cognitive benefit using the primary endpoint cognition (Brief Praxis Test [BPT]). Methods: Plasma and extracellular vesicle (EV; astrocytic and neuronal) biomarkers were assayed at baseline and 36 months (n = 138 each). Cognitive response was measured using combined scores from the BPT, vocabulary, and behavior and function DS tests. Support vector machine (SVM) analyses predicted diagnostic and treatment responders and change accuracy. Results: SVM classified demented versus non-demented with up to 99% accuracy and predicted treatment response and changes with up to 100% accuracy in plasma and EV. Discussion: Our study supports blood-based screening and precision diagnostics for AD therapy in DS.

TÍTULO / TITLE: - Intraindividual cognitive variability predicts amyloid beta, tau PET, and dementia conversion in Down syndrome: a potential marker of cognitive resilience

REVISTA / JOURNAL: - Alzheimers Dement. 2026 Jun;22(6):e71537. doi: 10.1002/alz.71537.

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AUTORES / AUTHORS: - Luciana Mascarenhas Fonseca et al.

INSTITUCIÓN / INSTITUTION: - The Krieger Klein Alzheimers Research Center, Rutgers Health, New Brunswick, New Jersey, USA

RESUMEN / SUMMARY: - Introduction: Adults with Down syndrome (DS) are at risk for Alzheimers disease (AD), yet identifying the preclinical phase remains challenging. Intraindividual cognitive variability (IICV) may be a sensitive marker of early AD-related changes but remains understudied in DS. Methods: Adults from the Alzheimers Biomarker Consortium-DS (ABC-DS) study (N = 460, mean age 43.3 years; 45.7% female) were included. Generalized linear models examined whether baseline IICV predicted incident mild cognitive impairment (MCI)/dementia, cognitive decline, and amyloid and tau positron emission tomography outcomes, adjusting for demographics, intellectual disability, apolipoprotein E ε4, site, assessment interval, and mean cognitive performance, with Bonferroni correction. Results: Greater IICV predicted incident MCI/dementia (odds ratio = 4.63 to 5.13, p < 0.05), greater amyloid burden, early tau accumulation, and higher tau across Braak stages, independent of mean cognition. Exploratory analyses suggested sex-specific interactions with tau outcomes. Discussion: IICV is a sensitive marker of dementia risk and cognitive resilience in DS, with potential utility for secondary prevention and trial enrichment.

TÍTULO / TITLE: - The tau biomarker cascade is condensed in Down syndrome compared with sporadic Alzheimers disease

REVISTA / JOURNAL: - Brain. 2026 Jul 7;149(7):2449-2462. doi: 10.1093/brain/awaf428. Free PMC article.

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AUTORES / AUTHORS: - Matthew D Zammit et al. Alzheimer Biomarker Consortium�Down Syndrome

INSTITUCIÓN / INSTITUTION: - Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.

RESUMEN / SUMMARY: - Characterizing the timing and progression of Alzheimers disease biomarker onset in Down syndrome (DS) and contrasting potential timing differences with neurotypical adults is needed to identify optimal Alzheimers disease therapeutic treatment windows in DS. In this study, 198 adults with DS from the Alzheimer Biomarker Consortium-Down Syndrome and 172 neurotypical adults from the Wisconsin Registry for Alzheimers Prevention with available longitudinal beta-amyloid PET, tau PET and plasma p-tau217 analysed on the Lilly Meso Scale Delivery Platform were included. Individuals with DS had a significantly higher lifetime risk of beta-amyloid plaque onset. Temporal modelling of longitudinal biomarker measures revealed earlier age at positivity of beta-amyloid plaques, p-tau217 and neurofibrillary tau tangles in DS relative to the neurotypical cohort. The onset of p-tau217 and tau PET positivity in DS occurred nearly simultaneously, roughly 4-6 years following beta-amyloid onset, whereas the neurotypical group displayed greater temporal latency between positivity of the two biomarkers. The early and simultaneous onset of these biomarkers in DS highlights the necessity for early therapeutic interventions in this population. This work, combined with the upcoming anti-amyloid safety and efficacy clinical trials for DS will help to identify optimal treatment windows for these individuals.

TÍTULO / TITLE: - Frequency of mixed neuropathologies in individuals with down syndrome with and without Alzheimers dementia

REVISTA / JOURNAL: - Acta Neuropathol. 2026 May 15;151(1):55. doi: 10.1007/s00401-026-03028-z. Free PMC article.

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AUTORES / AUTHORS: - Lisi Flores-Aguilar et al.

INSTITUCIÓN / INSTITUTION: - Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, 92697, USA

RESUMEN / SUMMARY: - Individuals with Down syndrome (DS) develop Alzheimers disease neuropathological change (ADNC) by the age of 40 years, and most develop dementia by their early 50s. The frequency of co-pathologies in clinically and neuropathologically characterized adults with DS has not been systematically characterized. We characterized the frequency of ADNC and common co-pathologies, including cerebral amyloid angiopathy (CAA), Lewy pathology (LP), limbic predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC), hippocampal sclerosis (HS), and other cerebrovascular and macroscopic findings reported in standardized National Alzheimers Coordinating Center (NACC) neuropathology forms in 63 adults with DS over 40 years. A secondary exploratory objective was to compare the neuropathological profiles between individuals with (n = 55) and without (n = 8) dementia from the same autopsy cohort. In the full autopsy cohort, cortical and hippocampal atrophy, and moderate-to-severe locus coeruleus hypopigmentation was a common finding. Pure ADNC, was present in only 29% of individuals. CAA was the most frequent co-pathology, present in approximately 84% of individuals followed by LP (21%), HS (19%), and LATE-NC (17%). Atherosclerosis and arteriolosclerosis were infrequent. In exploratory comparisons between dementia groups, brain weight was significantly lower in individuals with dementia than in those without (900 ± 116 vs 1060 ± 108 g P = .0006), and severe hippocampal atrophy and locus coeruleus hypopigmentation were more frequent in those with dementia (P = .049, P = .009, respectively). Advanced Braak NFT stage, frequent neuritic plaques, and high ADNC were more frequent in individuals with dementia (P = .0001, P = .03, P = .0016, respectively). LATE-NC and HS occurred exclusively in individuals with dementia, while LP and CAA were found in both groups. Individuals without dementia showed a less complex co-pathology profile than those with dementia. Our findings d

TÍTULO / TITLE: - Can Targeting Circadian Rhythms Help Prevent Alzheimer Disease?: Lessons From Down Syndrome

REVISTA / JOURNAL: - Neurology. 2026 May 26;106(10):e218086. doi: 10.1212/WNL.0000000000218086. Epub 2026 May 7. Free art

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AUTORES / AUTHORS: - Yi Fang , Yue Leng

INSTITUCIÓN / INSTITUTION: - From the Department of Psychiatry and Behavioral Sciences, University of California, San Francisco.

RESUMEN / SUMMARY: -

TÍTULO / TITLE: - Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimers disease in Down syndrome

REVISTA / JOURNAL: - Alzheimers Dement. 2026 May;22(5):e71498. doi: 10.1002/alz.71498. Free PMC article.

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AUTORES / AUTHORS: - Monika Rataj Baniowska et al.

INSTITUCIÓN / INSTITUTION: - Institut de Genetique Biologie Moleculaire et Cellulaire, IGBMC, UMR 7104- UMR-S 1258, Universite de Strasbourg, CNRS, Inserm, Illkirch, France.

RESUMEN / SUMMARY: - Introduction: Down syndrome (DS) is the leading genetic cause of intellectual disability and Alzheimers disease (AD), with over 90% of individuals developing AD-related dementia (DSAD). The triplication of the APP gene on chromosome 21 drives early amyloid-β (Aβ) accumulation, but other Hsa21 genes also contribute to pathology. Current DSAD models are limited by species-specific Aβ differences.Methods: We developed and characterized two novel DSAD mouse models with partial humanization of Aβ. Results: These models exhibit early AD features: cognitive deficits, hyperactivity, altered novelty and risk responses, tau hyperphosphorylation, and endolysosomal dysfunction. Amyloid precursor protein (APP) processing shifts toward β-secretase, increasing CTF-β and altering Aβ dynamics. Aβ humanization modulates behavior, improving specific cognitive tasks but enhancing anxiety traits. Myelinosome formation and impaired autophagic flux further align these models with human AD pathology. Discussion: They offer valuable tools to investigate early DSAD mechanisms and therapeutic strategies, pending development of a fully humanized trisomic model.

TÍTULO / TITLE: - Longitudinal Dynamics of the Blood Proteome Within the Alzheimer Spectrum in Down Syndrome

REVISTA / JOURNAL: - Neurology. 2026 Sep 22;107(6):e218494. Epub 2026 Sep 1.Free PMC article.

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AUTORES / AUTHORS: - Olivia Wagemann et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurology, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Germany.

RESUMEN / SUMMARY: - Background and objectives: Adults with Down syndrome (DS) have an increased risk of developing early Alzheimer disease. While our previous cross-sectional study investigated the blood proteome in the context of Alzheimer in DS, identifying CBLN4, CD14, C-X-C motif chemokine 17 (CXCL17), ectodysplasin A2 receptor (EDA2R), glial fibrillary acidic protein (GFAP), insulin-like growth factor binding protein-2 (IGFBP2), neurofilament light (NFL), SEPTIN3, and SPON1 as proteins of interest, longitudinal trajectories remain mostly unexplored. We aimed to characterize the longitudinal dynamics of these plasma proteins to evaluate their potential contribution to disease pathophysiology and associated cognitive decline. Methods: Adults with diagnosis of DS and ability to understand instructions of neuropsychological assessments were recruited at Ludwig Maximilians University Hospital Munich, returning for at least 1 annual follow-up visit for repeated clinical assessment, neuropsychological testing, and blood sample collection after baseline visit. Longitudinal blood protein dynamics were assessed using OLINK technology. Bayesian modeling analyzed longitudinal protein trajectories and their impact on cognitive performance. Spearman correlations of regression-derived rates of change investigated relationships between proteins and cognitive subdomains stratified by clinical diagnosis. Results: We included 59 adults with DS (46% female, median age = 32 years [interquartile range: 27-47]). All completed the first annual follow-up visit (median duration 13.37 months [12.35-20.95]), with 14 of them returning for a follow-up 2 visit (median 25.43 months [24.79-33.8]). Stratified analysis included 13 individuals with DS with (38% female, 54 years [49-58]) and 41 without diagnosis of cognitive decline (49% female, 29 years [24-35]). Cluster of differentiation 14, CXCL17, EDA2R, GFAP, IGFBP2, NFL, SEPTIN3, and SPON1 exhibited longitudinal increase, while CBLN4 decreased (all posterior d

TÍTULO / TITLE: - APOE and genetic risk variants influence Alzheimers disease onset in carriers of an extra copy of APP, with and without Down syndrome

REVISTA / JOURNAL: - Alzheimers Dement. 2026 Aug;22(8):e71738. doi: 10.1002/alz.71738. Free PMC article.

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AUTORES / AUTHORS: - Joan Groeneveld et al.

INSTITUCIÓN / INSTITUTION: - Genomics of Neurodegenerative Diseases and Aging, Human Genetics, Amsterdam UMC location VUmc, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

RESUMEN / SUMMARY: - Introduction: An extra copy of the amyloid precursor protein (APP) gene causes autosomal dominant Alzheimers disease (AD) and AD in Down syndrome (DS), but the factors underlying variability in age at onset (AAO) remain unclear. We investigated whether sporadic AD risk variants modify AAO. Methods: We analyzed clinical and genetic data from 100 APP duplication (APPdup) carriers and 957 individuals with DS. Cox models assessed associations of apolipoprotein E (APOE) ε2 and ε4 and the AD genetic risk score (AD-GRS; excluding APOE and chromosome 21 variants) with AAO. Results: Mean AAO was earlier in APPdup than DS (51 ± 7 vs. 53 ± 6 years; P = 0.0005). APOE ε2 delayed onset (hazard ratio [HR] = 0.47, P < 0.0001), whereas APOE ε4 (HR = 1.5, P = 0.0003) and higher AD-GRS (HR = 1.3 per standard deviation, P < 0.0001) accelerated onset. Predicted median AAO differed by 10 years between lowest and highest genetic risk. Discussion: Sporadic AD genetic risk factors are important modifiers of AAO in APPdup and DS, explaining part of the marked variability in onset.

TÍTULO / TITLE: - Characterizing circadian rest-activity rhythm patterns across Alzheimers disease continuum in Down syndrome

REVISTA / JOURNAL: - Alzheimers Dement. 2026 May;22(5):e71409. doi: 10.1002/alz.71409. Free PMC article.

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AUTORES / AUTHORS: - Sandra Gimenez et al.

INSTITUCIÓN / INSTITUTION: - Multidisciplinary Sleep Unit, Respiratory Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant, Pau (IIB SANT PAU), Barcelona, Spain

RESUMEN / SUMMARY: - Introduction: Sleep and circadian rest-activity rhythm (RAR) disruption may bidirectionally relate to Alzheimers disease (AD). Down syndrome (DS), the most common genetic cause of AD, presents sleep disorders, yet RAR patterns across the DS-associated AD continuum remain uncharacterized. Methods: We analyzed 7-day wrist actigraphy in 140 adults with DS (108 asymptomatic; 32 AD dementia) and 41 unimpaired controls. General linear models, adjusted for age, sex, sleep efficiency, and obstructive sleep apnea (OSA) severity, tested group differences, with interaction terms included to evaluate group-specific associations. Results: DS showed lower relative amplitude and higher nocturnal activity, already in asymptomatic individuals. Rhythm strength declined further with AD progression, while regularity and phase timing remained preserved until dementia. Findings were independent of sleep duration and OSA. Discussion: Adults with DS showed early RAR disturbance that progressed across the AD continuum, paralleling sporadic AD. Circadian RAR features may be scalable biomarkers of AD progression.

TÍTULO / TITLE: - New mouse models for Down syndrome Alzheimers disease

REVISTA / JOURNAL: - J Alzheimers Dis. 2026 Sep 17:13872877261488873. doi: 10.1177/13872877261488873. Online ahead of pri

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AUTORES / AUTHORS: - Frances K Wiseman

INSTITUCIÓN / INSTITUTION: - UK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK.

RESUMEN / SUMMARY: - In this issue Ishihara and colleagues report the development and characterization of new mouse models for Down syndrome Alzheimers disease, the most commonly occurring genetic cause of dementia worldwide. These new models add to the growing portfolio of in vivo models of Down syndrome. In particular, the new Ts1Kei-APPswe/PS1dE9 model may be highly useful for the study and identification of novel treatment targets for late onset myoclonic epilepsy of Down syndrome. This seizure disorder is a common comorbidity of Down syndrome Alzheimers disease affecting around half of all people with the condition and is associated with particularly adverse clinical outcomes.

TÍTULO / TITLE: - Alterations of gut microbiota in Down syndrome and their association with Alzheimers disease

REVISTA / JOURNAL: - Alzheimers Dement. 2026 Sep;22(9):e71815. doi: 10.1002/alz.71815. Free PMC article.

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AUTORES / AUTHORS: - Camilla Pellegrini et al.

INSTITUCIÓN / INSTITUTION: - IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

RESUMEN / SUMMARY: - Introduction: Adults with Down syndrome (DS) have a higher risk of Alzheimers disease (AD). As gut microbiota (GM) alterations have been reported in AD, we investigated their association with cognitive decline and plasma AD biomarkers in DS. Methods: Fecal and plasma samples were collected from 58 adults with DS (21-75 years) and 30 euploid controls (CTRL; 25-83 years). GM was profiled using 16S rRNA sequencing, filtering low prevalent taxa. Major neurocognitive disorder (NcD) was diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Plasma levels of phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured using Simoa. Results: DS showed no changes in overall microbial diversity compared to CTRL, but genera including UBA1819 and Intestinibacter were altered. Specific genera showed changes in DS with NcD, like Alistipes (increased) and Roseburia (decreased), with the latter negatively associated with plasma AD biomarkers. Discussion: Adults with DS display AD-associated changes in GM partially resembling those reported previously in euploid AD patients.

Cardiology - Cardiología

TÍTULO / TITLE: - Obesity and cardiovascular risk in down syndrome: Challenges and updated management

REVISTA / JOURNAL: - Curr Probl Cardiol. 2026 Oct;51(10):103372. doi: 10.1016/j.cpcardiol.2026.103372. Epub 2026 May 15.

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AUTORES / AUTHORS: - Aditya Lumb et al.

INSTITUCIÓN / INSTITUTION: - Faculty of Health Sciences, School of Medicine, Queens University, Kingston, Ontario, Canada

RESUMEN / SUMMARY: - Down syndrome (DS) or trisomy 21 is a genetic condition presenting with intellectual disabilities, distinctive phenotypic features, and multisystem involvement. As life expectancy in individuals with DS increases, obesity has emerged as a significant and growing clinical concern. Although obesity is highly prevalent among DS patients, its contribution in shaping cardiovascular risk has not been comprehensively synthesized in the existing literature. Studies published between January 2000 and March 2026 were identified through searches of PubMed and ScienceDirect, supplemented by manual screening of reference lists. In total, 65 studies met the inclusion criteria. Evidence indicates that individuals with DS commonly exhibit increased central adiposity, altered metabolic and adipokine profiles, adverse lipid abnormalities, sedentary behavior, and a higher prevalence of sleep apnea, all of which may contribute to downstream cardiometabolic and cardiovascular strain. However, findings on insulin resistance remain varied, and much of the available evidence is cross-sectional and based on intermediate risk markers rather than on longitudinal cardiovascular outcomes. Overall, the current literature supports obesity in DS as a clinically relevant and probable amplifier of cardiovascular risk. Early, targeted strategies centred on nutrition, physical activity, and caregiver-supported interventions may help mitigate long-term burden. Although DS-specific longitudinal and interventional studies remain needed.

TÍTULO / TITLE: - Converging signalling disruptions: a threshold for Down syndrome hearts

REVISTA / JOURNAL: - Trends Mol Med. 2026 Aug;32(8):735-738. doi: 10.1016/j.molmed.2026.05.002. Epub 2026 Jun 9. Free ar

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AUTORES / AUTHORS: - Mariel Schwietzer et al.

INSTITUCIÓN / INSTITUTION: - Vascular Signalling, Molecular Cardiology, Department of Cardiology I-Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Münster, Münster, Germany.

RESUMEN / SUMMARY: - Why do half of all children with Down syndrome have heart defects? Recent studies show that multiple chromosome 21 genes-most notably the chromatin regulator high-mobility group nucleosome-binding domain 1-collectively disrupt bone morphogenetic protein, Wingless/Integrated, Neurogenic locus notch homolog, and calcineurin-nuclear factor of activated T cells signalling. In this forum, we propose a convergent threshold model for these cardiac malformations.

Ear/Nasal - Otorrinolaringología

TÍTULO / TITLE: - Long-term outcome after adenotonsillectomy in Down Syndrome with OSAS

REVISTA / JOURNAL: - Braz J Otorhinolaryngol 2026 Sep-Oct;92(5):101883. Epub 2026 Sep 2. Free PMC article.

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AUTORES / AUTHORS: - Sara Costa Gomes et al.

INSTITUCIÓN / INSTITUTION: - Universiteit Gent (UGent), University Hospital of Ghent (UZ Gent), Department of Otorhinolaryngology, Ghent, Belgium

RESUMEN / SUMMARY: - Objectives: The study aimed to evaluate short- and long-term polysomnographic parameters in children with Down Syndrome (DS) and Obstructive Sleep Apnea Syndrome (OSAS) submitted to surgical therapy. Secondarily, this study also aimed to describe how other congenital comorbidities influence sleep patterns and to present trends in Body Mass Index (BMI) percentile/Z-score after adenotonsillectomy in DS population. Methods: Longitudinal retrospective-cohort study of children with Down syndrome and respiratory sleep disorders. Patients with habitual snoring that underwent polysomnographic exams and surgical therapy were included (n = 54). We excluded patients >18-years old by the time of the surgery and who presented diagnostic polysomnography with Total Sleep Time (TST) <180 min, ending in a group of 25 children. The post-therapy parameters were divided in short- (<18-months) and long-term (>18-months) results, as heterogeneity in follow-up intervals occurred. Results: Of the 25 subjects, the short- and long-term Obstructive Apnea-Hypopnea Index (OAHI) were both significantly different from the pre-surgery value. However, there is also a difference between the short- and long-term OAHI post-surgery (p < 0.001). Children with laryngomalacia present the highest OAHI mean pre-surgery (56.7 ± 13.8). Conclusions: Adeno/tonsillectomy for children with DS and OSAS brings a significant lowering on OAHI in a short- and long-term post-surgical follow-up, although long-term OAHI is significantly higher than the short-term. An extended polysomnographic post-surgical follow-up should be recommended. Due to the study limitations, further studies are still needed to clarify the best practice for this specific population.

TÍTULO / TITLE: - Lingual Tonsillectomy for Resistant Obstructive Sleep Apnea in Children with Down Syndrome: A Systematic Review and Meta-Analysis

REVISTA / JOURNAL: - Ann Otol Rhinol Laryngol. 2026 Jun;135(6):429-435. Epub 2026 Jan 3. Free PMC article.

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AUTORES / AUTHORS: - Emma Finnegan et al.

INSTITUCIÓN / INSTITUTION: - School of Medicine, Trinity College Dublin, Ireland.

RESUMEN / SUMMARY: - Introduction: Obstructive sleep apnea (OSA) affects many children, particularly those with Down syndrome (DS), with prevalence estimates ranging from 50% to 100%. Although adenotonsillectomy is the traditional first-line treatment, individuals with DS frequently have residual OSA (rOSA) because to their complex airway architecture. Lingual tonsil hypertrophy has been found as a significant risk factor for rOSA; however, the role of lingual tonsillectomy (LT) in this population is uncertain. Methods: We conducted a systematic review and meta-analysis according to PRISMA and Cochrane guidelines, registered with PROSPERO (CRD42024552955). We included studies of pediatric patients (≤18 years) with DS and rOSA who underwent LT. Primary outcomes were changes in apnea-hypopnea index (AHI), obstructive AHI (OAHI), and oxygen nadir (O₂). Secondary outcomes included postoperative complications. Results: Three retrospective case series comprising 68 patients met the inclusion criteria. Pooled analysis demonstrated a mean improvement in oxygen nadir of 4.58% (95% CI: 2.73-6.43, I2 = 0%). AHI and OAHI scores were decreased by -2.97 (95% CI: -8.88 to 2.94, I2 = 24%) and -8.20 (95% CI: -13.46 to -2.94, I2 = 0%) respectively. Complication rates were low but inconsistently reported. Conclusion: Lingual tonsillectomy appears effective in improving OSA severity in children with DS. While promising, outcome improvements may be less pronounced than in the general population, likely due to complex anatomical and physiological factors unique to this group. Standardized outcome measures and prospective studies are needed to better guide management in this high-risk group.

Endocrinology/Nutrition - Endocrinología/Nutrición

TÍTULO / TITLE: - Creatine supplementation modifies fat deposition in arm and leg tissues in individuals with Down syndrome

REVISTA / JOURNAL: - Nutrition. 2026 Jul:147:113175. doi: 10.1016/j.nut.2026.113175. Epub 2026 Feb 21.

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AUTORES / AUTHORS: - Aleksandro Belo Ferreira et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, SP, Brazil; Department of Pediatrics, Elo21 Gestao em Saude e Treinamento, Sao Paulo, SP, Brazil.

RESUMEN / SUMMARY: - Background: Individuals with Down syndrome (DS) are at increased risk for obesity, sarcopenia, and metabolic disorders, highlighting the need for safe and effective strategies to improve body composition. Objective: To evaluate the effects of creatine supplementation on body composition and metabolic safety markers in individuals with DS. Methods: In this prospective, randomized, double-blind study, 50 participants with DS received either oral creatine supplementation (20 g/d for 5 d, followed by 5 g/d for 6 mo) or placebo (dextrose). Dual-energy x-ray absorptiometry (DXA) was used to assess body composition, and laboratory tests monitored renal and hepatic function at baseline and after six months. Results: After 6 mo, the creatine group exhibited a significant reduction in regional fat percentage in the arms and legs compared with placebo, particularly among females, without adverse effects on renal or hepatic biomarkers. No significant changes were observed in total fat or lean mass. Conclusion: During the study, creatine supplementation was found to be safe and to promote a selective reduction in regional adiposity in individuals with DS. These results indicate that creatine is a promising, low-cost way of improving body composition in this vulnerable group. However, further research combining supplementation with exercise interventions is recommended.

TÍTULO / TITLE: - Obesity and cardiovascular risk in down syndrome: Challenges and updated management

REVISTA / JOURNAL: - Curr Probl Cardiol. 2026 Oct;51(10):103372. doi: 10.1016/j.cpcardiol.2026.103372. Epub 2026 May 15

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AUTORES / AUTHORS: - Aditya Lumb et al.

INSTITUCIÓN / INSTITUTION: - Faculty of Health Sciences, School of Medicine, Queens University, Kingston, Ontario, Canada

RESUMEN / SUMMARY: - Down syndrome (DS) or trisomy 21 is a genetic condition presenting with intellectual disabilities, distinctive phenotypic features, and multisystem involvement. As life expectancy in individuals with DS increases, obesity has emerged as a significant and growing clinical concern. Although obesity is highly prevalent among DS patients, its contribution in shaping cardiovascular risk has not been comprehensively synthesized in the existing literature. Studies published between January 2000 and March 2026 were identified through searches of PubMed and ScienceDirect, supplemented by manual screening of reference lists. In total, 65 studies met the inclusion criteria. Evidence indicates that individuals with DS commonly exhibit increased central adiposity, altered metabolic and adipokine profiles, adverse lipid abnormalities, sedentary behavior, and a higher prevalence of sleep apnea, all of which may contribute to downstream cardiometabolic and cardiovascular strain. However, findings on insulin resistance remain varied, and much of the available evidence is cross-sectional and based on intermediate risk markers rather than on longitudinal cardiovascular outcomes. Overall, the current literature supports obesity in DS as a clinically relevant and probable amplifier of cardiovascular risk. Early, targeted strategies centred on nutrition, physical activity, and caregiver-supported interventions may help mitigate long-term burden. Although DS-specific longitudinal and interventional studies remain needed.

TÍTULO / TITLE: - Early metabolic and hepatic alterations in children with Down syndrome: a hidden risk beyond BMI

REVISTA / JOURNAL: - J Pediatr Endocrinol Metab. 2026 Jun 1;39(7):638-647. doi: 10.1515/jpem-2026-0221. Print 2026 Jul 24

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AUTORES / AUTHORS: - Valeria Calcaterra et al.

INSTITUCIÓN / INSTITUTION: - Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, Pavia, Italy.

RESUMEN / SUMMARY: - Objectives: Children and adolescents with Down syndrome (DS) are at increased risk of cardiometabolic impairment, but this vulnerability may not be adequately captured by body mass index (BMI) alone. This study aimed to characterize anthropometric, metabolic, and hepatic alterations in pediatric DS beyond conventional BMI-based assessment. Methods: We included 95 children and adolescents aged 5-18 years: 48 with DS and 47 controls. Anthropometric assessment included weight, height, waist circumference, BMI z-score, waist-to-height ratio (WHtR), and predicted body composition. Fasting blood samples were analyzed for glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride-glucose (TyG) index, lipid profile, and liver enzymes. Between-group differences were assessed using age- and sex-adjusted analysis of covariance, while multivariate analyses identified the variables contributing most strongly to group discrimination. Results: Compared with controls, children with DS showed no significant difference in BMI z-score, but had higher WHtR and % fat mass and lower % fat-free mass (p<0.05). They also exhibited a less favorable metabolic profile, with higher fasting glucose, HOMA-IR, and TyG index, lower HDL-cholesterol, higher triglycerides, and higher liver enzyme levels (p<0.05). Multivariate analyses confirmed that liver enzymes, glycemic markers, HDL-cholesterol, and WHtR were the strongest contributors to group separation. Conclusions: Children and adolescents with DS display an early high-risk cardiometabolic phenotype characterized by altered body composition, insulin resistance, dyslipidemia, and biochemical signs of hepatic involvement only partly reflected by BMI. These findings support broader metabolic surveillance in pediatric DS to improve early risk stratification and guide preventive interventions.

Epidemiology - Epidemiología

TÍTULO / TITLE: - Impact of National Screening Programs on Down syndrome prevalence and outcomes

REVISTA / JOURNAL: - Acta Obstet Gynecol Scand. 2026 Apr;105(4):613-620. doi: 10.1111/aogs.70157. Epub 2026 Feb 13. Free

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AUTORES / AUTHORS: - Cecilie Bryn Nordklev et al

INSTITUCIÓN / INSTITUTION: - Fetal Medicine Centre, Oslo University Hospital, Oslo, Norway

RESUMEN / SUMMARY: - Introduction: Over the past five decades, antenatal screening programs have evolved significantly, primarily through advancements in ultrasound technology and the shift from invasive to non-invasive prenatal testing methods. This study aimed to evaluate the impact of these developments in prenatal screening for Down syndrome (DS) on the prevalence of live and stillbirths, as well as terminations of pregnancy (TOP) with DS. Material and methods: This population-based registry study included all pregnancies in Norway from 1967 to 2021, with data on TOPs available from 1999. Information on DS pregnancies was obtained from the Medical Birth Registry of Norway. Logistic regression models were applied to evaluate time trends and maternal characteristics associated with TOP. Results: Among 3 231 159 pregnancies, 4764 (0.147%) were affected by DS. The prevalence of DS pregnancies increased from 0.165% in 1999 to 0.251% in 2021. During this period, the proportion of TOP rose from 20% to 55%, while prenatal detection rates improved from 18% to 70%. Despite increased detection, the proportion of TOP following prenatal diagnosis remained stable at approximately 80%. The prevalence of live births with DS remained stable at approximately 0.106%, while the prevalence of stillbirths was around 0.008%. Maternal age, parity, country of birth, and region of residence were associated with TOP decisions. Mean gestational age at termination decreased from 17.5 to 15.7 weeks. Conclusions: Over recent decades, prenatal detection and termination of DS pregnancies have increased. However, the proportion of women continuing pregnancies after a prenatal diagnosis and the prevalence of live- and stillbirths with DS have remained stable.

Gastroenterology - Gastroenterología

TÍTULO / TITLE: - Altered hepatic metabolism in Down syndrome

REVISTA / JOURNAL: - Cell Rep. 2026 Jan 27;45(1):116835. doi: 10.1016/j.celrep.2025.116835. Epub 2026 Jan 14. Free PMC a

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AUTORES / AUTHORS: - Lauren N Dunn et al.

INSTITUCIÓN / INSTITUTION: - Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz, Aurora, CO 80045, USA.

RESUMEN / SUMMARY: - Trisomy 21 (T21) gives rise to Down syndrome (DS), the most commonly occurring chromosomal abnormality in humans. T21 affects nearly every organ and tissue system in the body, predisposing individuals with DS to congenital heart defects, autoimmunity, and Alzheimers disease, among other co-occurring conditions. Here, using multi-omic analysis of plasma from more than 400 people, we report broad metabolic changes in the population with DS typified by increased bile acid levels and protein signatures of liver dysfunction. In a mouse model of DS, we demonstrate conservation of perturbed bile acid metabolism accompanied by liver pathology. Bulk RNA sequencing revealed widespread impacts of the Dp16 model on hepatic metabolism and inflammation, while single-cell transcriptomics highlighted cell types associated with these observations. Modulation of dietary fat profoundly impacted gene expression, bile acids, and liver pathology. Overall, these data represent evidence for altered hepatic metabolism in DS that could be modulated by diet.

TÍTULO / TITLE: - A systematic review of celiac disease recommendations for children with Down syndrome

REVISTA / JOURNAL: - J Pediatr Gastroenterol Nutr. 2026 Aug;83(2):304-313. doi: 10.1002/jpn3.70469. Epub 2026 May 29. Fr

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AUTORES / AUTHORS: - Vanessa Nadia Dargenio et al.

INSTITUCIÓN / INSTITUTION: - Interdisciplinary Department of Medicine, Pediatric Section, Childrens Hospital Giovanni XXIII, University of Bari "Aldo Moro", Bari, Italy.

RESUMEN / SUMMARY: - This systematic review critically compares current international guidelines and recommendations from major medical organizations on the management of celiac disease (CD) in individuals with Down syndrome (DS), in light of the increased disease prevalence and the diagnostic challenges posed by overlapping clinical and immunological features. A comprehensive search of PubMed, Embase, Scopus, and international association websites (through June 1, 2025) identified guidelines, position papers, and expert statements endorsed by national or international bodies. Two reviewers independently screened and selected studies, and guideline quality was assessed using the AGREE II tool. Of 929 records identified, seven clinical practice guidelines, and two clinical practice reports were included. Recommendations varied widely, ranging from universal screening (e.g., British Society of Paediatric Gastroenterology, Hepatology and Nutrition [BSPGHAN], Down Syndrome Medical Interest Group [DSMIG], European Society for the Study of Coeliac Disease [ESsCD], European Society for Pediatric Gastroenterology, Hepatology, and Nutrition [ESPGHAN] and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition [NASPGHAN]) to symptom-based testing (e.g., American Academy of Pediatrics [AAP], American Gastroenterological Association [AGA], American College of Gastroenterology [ACG], and National Institute for Health and Care Excellence [NICE]). While there is consensus on serologic screening using tissue transglutaminase IgA (tTG-IgA) and total IgA, interpretation is complicated by the high prevalence of selective IgA deficiency in DS, often necessitating IgG-based testing. HLA genotyping is not generally recommended for routine screening but may help exclude CD in non-susceptible individuals and support biopsy-sparing diagnostic pathways. In conclusion, marked heterogeneity exists among current guidelines. Harmonized, evidence-based recommendations are needed. HLA-DQ2/DQ8

TÍTULO / TITLE: - Early metabolic and hepatic alterations in children with Down syndrome: a hidden risk beyond BMI

REVISTA / JOURNAL: - J Pediatr Endocrinol Metab. 2026 Jun 1;39(7):638-647. doi: 10.1515/jpem-2026-0221. Print 2026 Jul 24

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AUTORES / AUTHORS: - Valeria Calcaterra et al.

INSTITUCIÓN / INSTITUTION: - Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, Pavia, Italy.

RESUMEN / SUMMARY: - Objectives: Children and adolescents with Down syndrome (DS) are at increased risk of cardiometabolic impairment, but this vulnerability may not be adequately captured by body mass index (BMI) alone. This study aimed to characterize anthropometric, metabolic, and hepatic alterations in pediatric DS beyond conventional BMI-based assessment. Methods: We included 95 children and adolescents aged 5-18 years: 48 with DS and 47 controls. Anthropometric assessment included weight, height, waist circumference, BMI z-score, waist-to-height ratio (WHtR), and predicted body composition. Fasting blood samples were analyzed for glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride-glucose (TyG) index, lipid profile, and liver enzymes. Between-group differences were assessed using age- and sex-adjusted analysis of covariance, while multivariate analyses identified the variables contributing most strongly to group discrimination. Results: Compared with controls, children with DS showed no significant difference in BMI z-score, but had higher WHtR and % fat mass and lower % fat-free mass (p<0.05). They also exhibited a less favorable metabolic profile, with higher fasting glucose, HOMA-IR, and TyG index, lower HDL-cholesterol, higher triglycerides, and higher liver enzyme levels (p<0.05). Multivariate analyses confirmed that liver enzymes, glycemic markers, HDL-cholesterol, and WHtR were the strongest contributors to group separation. Conclusions: Children and adolescents with DS display an early high-risk cardiometabolic phenotype characterized by altered body composition, insulin resistance, dyslipidemia, and biochemical signs of hepatic involvement only partly reflected by BMI. These findings support broader metabolic surveillance in pediatric DS to improve early risk stratification and guide preventive interventions.

Genetics - Genética

TÍTULO / TITLE: - Promoting Research Excellence in Down Syndrome: Proceedings of the 5th International Conference of the Trisomy 21 Research Society

REVISTA / JOURNAL: - Neuromolecular Med. 2026 Jun 6;28(1):34. doi: 10.1007/s12017-026-08921-0. Free PMC article.

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AUTORES / AUTHORS: - Fabio Di Domenico et al.

INSTITUCIÓN / INSTITUTION: - Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.

RESUMEN / SUMMARY: - Down syndrome (DS), or trisomy 21 (T21), represents the most common genetic cause of intellectual disability worldwide and is associated with a wide range of medical, developmental, and neurodegenerative conditions, including a universal predisposition to early-onset Alzheimers disease (AD). Since its establishment in 2014, the Trisomy 21 Research Society (T21RS) has provided a global forum for advancing DS research across disciplines and promoting translational efforts to improve health and quality of life. Every two years, T21RS hosts an international scientific meeting that brings together researchers, clinicians, self-advocates, families, and industry stakeholders. In 2024, the 5th T21RS International Conference was held in Rome, Italy, from June 5 to 8, under the theme "Promoting Research Excellence in Down Syndrome." The meeting brought together about 500 scientists from 26 countries across five continents, and more than 900 attendees overall, including families and caregivers. The scientific program featured 5 keynote lectures, 2 satellite meetings, 17 symposia, 7 nano symposia, 2 workshops, and 1 industry-focused session, totaling more than 150 oral presentations. More than 230 abstracts were presented as posters. The conference covered research across the lifespan of individuals with DS, spanning genomic and epigenetic regulation, molecular and cellular mechanisms, preclinical and experimental models, cognition and behavior, neurodevelopment, aging and neurodegeneration, co-occurring medical conditions, and therapeutic interventions. Dedicated sessions focused on capacity-building in DS research and societal engagement were established. Significantly, T21RS promoted inclusivity by supporting 60 young investigator fellowships, providing childcare awards, and organizing a two-day program for families and caregivers in collaboration with Italian DS associations. This proceeding summarizes the main scientific highlights of the 5th T21RS International Conference

TÍTULO / TITLE: - A single-cell multiomic analysis identifies molecular and gene-regulatory mechanisms dysregulated in developing Down syndrome neocortex

REVISTA / JOURNAL: - Science. 2026 Apr 23;392(6796):eaea1259. doi: 10.1126/science.aea1259. Epub 2026 Apr 23. Free PMC ar

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AUTORES / AUTHORS: - Celine K Vuong et al.

INSTITUCIÓN / INSTITUTION: - Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common genetic cause of intellectual disability, yet the cellular and molecular mechanisms driving this developmental disorder remain unclear. In this study, we profiled human mid-gestation neocortex with snMultiomics across 26 donors. We observed a reduction in neural progenitors and corticothalamic neurons and an increase of intratelencephalic neurons, accompanied by accelerated neuronal specification. We uncovered widespread changes in gene expression, chromatin accessibility, and cell interaction networks affecting neurogenesis, specification, and maturation; and in gene-regulatory networks directing these processes, including those downstream of human chromosome 21 (HSA21)-encoded genes. We identified cell-specific molecular pathways shared with other neurodevelopmental disorders and enrichment of genome-wide association study signals in DS-altered chromatin. Together, our data revealed a cascade of molecular dysregulation outlining the earliest steps in DS, providing a foundation for future therapeutic targets.

TÍTULO / TITLE: - Systematic multi-omic deconvolution of the clinical heterogeneity of Down syndrome

REVISTA / JOURNAL: - Nat Commun. 2026 May 11;17(1):6312. doi: 10.1038/s41467-026-72946-z. Free PMC article.

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AUTORES / AUTHORS: - Micah G Donovan et al.

INSTITUCIÓN / INSTITUTION: -

RESUMEN / SUMMARY: - Persons with Down syndrome, the genetic condition caused by trisomy 21, are at high risk of developing various co-occurring conditions affecting all major organ systems. Recent multi-omic studies have revealed the profound impacts of trisomy 21 on human biology, including strong effects on the transcriptome, proteome, metabolome, and immunome. However, it is unclear whether these changes are conserved effects of trisomy 21 versus effects associated with specific co-occurring conditions. Here we report a multi-omic investigation of 100 clinical phenotypes in a cohort of 356 individuals with Down syndrome, which identifies many phenotype-associated signatures of potential clinical significance. Obesity associates with the largest number of changes in the proteome and metabolome of persons with Down syndrome, with dysregulation of key hormonal, growth signaling, and neurotransmitter systems. Congenital heart defects associate with the strongest changes in the whole blood transcriptome, concurrent with interferon hyperactivity and immune remodeling. Key signatures dysregulated by trisomy 21 are exacerbated in those with seizure disorders, gastrointestinal conditions, and various cardiopulmonary diseases. These analyses implicate immune dysregulation as a driver of diverse clinical phenotypes in Down syndrome beyond canonical autoimmune disorders. Altogether, these results support the development of personalized medicine approaches for the clinical management of Down syndrome.

TÍTULO / TITLE: - Early dynamics of the genome in Down syndrome

REVISTA / JOURNAL: - Science. 2026 Apr 23;392(6796):360-361. doi: 10.1126/science.aeh0065. Epub 2026 Apr 23.

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AUTORES / AUTHORS: - Tarik Haydar, Zhen Li

INSTITUCIÓN / INSTITUTION: - Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA.

RESUMEN / SUMMARY: - Cell type-specific early hallmarks of Down syndrome are uncovered.

TÍTULO / TITLE: - Identification of the Down Syndrome Critical Region 3 Gene as a Mammalian Cell Size Regulator

REVISTA / JOURNAL: - Genes Cells. 2026 Sep;31(5):e70142. doi: 10.1111/gtc.70142. Free PMC article

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AUTORES / AUTHORS: - Kazumi Kimura et al.

INSTITUCIÓN / INSTITUTION: - Division of Cell Function Research Support, Biomedical Research Support Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

RESUMEN / SUMMARY: - Using a genetic screening approach based on an inducible gene-activating system and cell sorting, Down syndrome critical region 3 (DSCR3) was isolated as a gene whose overexpression increased cell size. Fibroblasts derived from individuals with Down syndrome (DS) exhibit elevated DSCR3 expression at both the mRNA and protein levels, correlating with increased cell volume compared to fibroblasts from healthy donors. Despite a slower proliferation rate, DS fibroblasts demonstrate higher basal and maximal mitochondrial respiration, suggesting enhanced metabolic activity associated with increased cell size. siRNA-mediated knockdown of DSCR3 reduces cell size in both DS and normal fibroblasts, indicating its general role in cell size regulation. As DSCR3 is a component of the retriever complex involved in endosomal cargo recycling, these findings position membrane protein trafficking as a novel module for cell size control.

Hematology/Oncology - Hematología/Oncología

TÍTULO / TITLE: - CPX-351 in Down syndrome-associated myeloid leukemia: results and prognostic factors from the phase 3 ML-DS 2018 trial

REVISTA / JOURNAL: - Blood. 2026 Jan 15;147(3):229-240. doi: 10.1182/blood.2025030775. Free PMC article

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AUTORES / AUTHORS: - Stephanie Laszig et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Goethe-University Frankfurt, Frankfurt, German

RESUMEN / SUMMARY: - Myeloid leukemia of Down syndrome (ML-DS) is associated with an excellent prognosis but high treatment-related toxicity and mortality. The Phase 3 Clinical Trial for CPX-351 in ML-DS 2018 aimed to maintain the excellent event-free survival (EFS) achieved in the previous ML-DS 2006 trial while reducing the treatment intensity. Intensity-reduced induction and reinduction therapy with cytarabine and idarubicin with or without etoposide was replaced with CPX-351 (66 U/m2 on 3 days in course 1 and on 2 days in course 2). Risk stratification was based on flow cytometric measurable residual disease (MRD) after first induction. High-risk patients received high-dose cytarabine (3 g/m2 per 12 hour) in consolidation; standard-risk patients received cytarabine at a dose of 1 g/m2 per 12 hour. A total of 35 patients were enrolled until the trial was halted because of an unexpectedly high relapse rate. A per-protocol interim analysis revealed a significantly lower 24-month EFS when compared with the ML-DS 2006 trial (69% vs 90%; P< .001). In contrast with previous studies, most patients who relapsed responded to salvage therapy, leading to a comparable 24-month overall survival of 88% (vs 92%; P = .612). CPX-351 demonstrated a favorable toxicity profile with no treatment-related mortality. Positive MRD by error-corrected GATA1 next-generation sequencing, the presence of trisomy 8 or a complex karyotype were associated with an increased risk for relapse. In conclusion, replacing intensity-reduced induction therapy with CPX-351 in ML-DS led to a significantly lower EFS, highlighting the need for dose optimization to balance the efficacy and toxicity in this sensitive patient population. This trial was registered at https://www.clinicaltrialsregister.eu as EudraCT #2018-002988-25.

TÍTULO / TITLE: - DLK1 is a GATA1s-driven dependency and therapeutic target in Down syndrome-associated myeloid leukemia

REVISTA / JOURNAL: - Blood Adv. 2026 Jun 23;10(12):4120-4133. doi: 10.1182/bloodadvances.2025018830. Free PMC article.

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AUTORES / AUTHORS: - Lonneke J Verboon et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany.

RESUMEN / SUMMARY: - Children with Down syndrome have a markedly increased risk of developing myeloid leukemia. Although having an excellent prognosis, 10% to 20% develop relapsed or refractory disease with poor survival, highlighting the need for new targeted approaches. The pathogenesis of myeloid leukemia of Down syndrome (ML-DS) is tightly linked to fetal hematopoiesis and mutations in GATA1, generating the truncated GATA1 short (GATA1s) isoform. We identified Delta-like noncanonical Notch ligand 1 (DLK1) as a direct GATA1s target. DLK1, a paternally imprinted transmembrane protein, is highly expressed in fetal liver CD34+ cells but absent in adult hematopoiesis, making it an attractive immunotherapeutic target. Chromatin profiling revealed GATA1s occupancy at a distal enhancer within the DLK1-DIO3 locus, driving aberrant DLK1 upregulation in ML-DS. Functional studies demonstrated that DLK1 is a leukemia dependency, as its genetic ablation impaired proliferation and engraftment, induced apoptosis, and altered Notch and β-catenin signaling. Therapeutically, a DLK1-directed antibody-drug conjugate-induced selective cytotoxicity, abrogated colony formation, and significantly prolonged survival in refractory ML-DS patient-derived xenograft (PDX) models, achieving durable remissions at higher doses. These findings establish DLK1 as a leukemia-specific vulnerability and provide preclinical proof-of-concept for DLK1-targeted therapies in ML-DS and other leukemias with fetal-like expression programs.

TÍTULO / TITLE: - Single cell transcriptional evolution of myeloid leukemia of Down syndrome

REVISTA / JOURNAL: - Nat Commun. 2026 Apr 23;17(1):3474. doi: 10.1038/s41467-026-71707-2. Free PMC article.

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AUTORES / AUTHORS: - Mi K Trinh et al.

INSTITUCIÓN / INSTITUTION: - Wellcome Sanger Institute, Hinxton, UK.

RESUMEN / SUMMARY: - Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS). Unusually for a childhood leukaemia, ML-DS arises from a preleukaemic state, termed transient abnormal myelopoiesis (TAM), via a conserved sequence of mutations. Here, we examine the relationship between the genetic and transcriptional evolution of ML-DS from natural variation; a rich collection of primary patient samples and foetal tissues with a range of constitutional karyotypes. We distil transcriptional consequences of each genetic step in ML-DS evolution, utilising single-cell mRNA sequencing, complemented by phylogenetic analyses in progressive disease. We find that transcriptional changes induced by the TAM-defining GATA1 mutations are retained in, and account for most of the ML-DS transcriptome. The GATA1 transcriptome pervades all stages of ML-DS, including progressive disease that had undergone genetic evolution. Our approach delineates the transcriptional evolution of ML-DS and provides an analytical blueprint for distiling consequences of mutations within their pathophysiological context.

TÍTULO / TITLE: - Polycomb repressive complex 2 insufficiency underlies myeloid leukemia in Down syndrome

REVISTA / JOURNAL: - Blood. 2026 Jul 23;148(4):462-476. doi: 10.1182/blood.2025032083.

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AUTORES / AUTHORS: - Yutaro Suzuki et al.

INSTITUCIÓN / INSTITUTION: - Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

RESUMEN / SUMMARY: - Children with Down syndrome (DS) have an elevated risk of developing myeloid leukemia (ML; ML in DS [ML-DS]). In addition to mutations in GATA1, which generate the truncated isoform GATA1-short (GATA1s), ML-DS requires additional somatic gene mutations, most frequently in cohesion and Polycomb repressive complex 2 (PRC2) genes. Here, we show that PRC2 insufficiency underlies ML-DS pathogenesis. Transplantation of Gata1s fetal liver cells followed by deletion of the cohesion subunit Stag2 and/or the PRC2 component Ezh2 induced megakaryocyte-biased differentiation and expansion of megakaryocytic progenitors, culminating in lethal myelofibrosis. Mechanistically, loss of Stag2 or Ezh2 reinforced Gata1s-driven reduced chromatin accessibility at erythroid transcription factor target loci in premegakaryocyte/erythroid progenitors (pre-MegEs), thereby promoting megakaryocytic skewing. Ezh2 loss attenuated the Gata1s-mediated global elevation of H3K27 trimethylation in pre-MegEs, resulting in derepression of a broad set of PRC2 target genes and establishing a functionally PRC2-insufficient state. Similarly, Stag2 loss induced a moderate but significant degree of PRC2-insufficient state in Gata1s progenitors. Furthermore, chromosome 21-encoded miR-125b blocked megakaryocytic differentiation of Gata1s progenitors lacking either Stag2 or Ezh2 alone but drove full transformation and expansion of CD150+Sca-1+c-Kit+ leukemic stem cell-like populations only upon concurrent loss of both Stag2 and Ezh2, leading to acute megakaryoblastic leukemia in mice. These findings reveal that cohesin and PRC2 insufficiencies converge on PRC2 dysfunction while exerting distinct epigenetic effects and synergize with trisomy 21 and GATA1s to remodel the epigenetic landscape, driving progression from a preleukemic state to overt leukemia.

TÍTULO / TITLE: - Molecular risk markers define risk of relapse in myeloid leukemia of Down syndrome beyond measurable residual disease

REVISTA / JOURNAL: - Blood Adv. 2026 Mar 10;10(5):1576-1586. doi: 10.1182/bloodadvances.2025017837. Free PMC article.

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AUTORES / AUTHORS: - Jason N Berman et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, University of Ottawa Childrens Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada

RESUMEN / SUMMARY: - Myeloid leukemia of Down syndrome (ML-DS) is a distinct form of pediatric acute myeloid leukemia (AML) that responds to reduced-intensity chemotherapy, as compared with non-DS AML that requires intensive chemotherapy and often stem cell transplant. While most patients with ML-DS have a favorable prognosis, outcomes for those with refractory or relapsed disease are dismal. Childrens Oncology Group study AAML1531 introduced the use of measurable residual disease by multiparameter flow cytometry at the end of the first course of induction therapy (EOI-1 MRD) for risk stratification of treatment intensity. Of 280 patients with ML-DS who were enrolled, 41 were classified as high risk (HR) due to positive EOI-1 MRD, and treated with intensified chemotherapy similar to that used for pediatric non-DS AML. Treatment intensification did not improve the 2-year event-free survival compared with patients who were MRD-positive treated with reduced-intensity therapy in the predecessor study AAML0431 (80.5% ± 12.4% vs 76%; P = .247) or overall survival (80.5% ± 12.4% vs 76.2% ± 18.6%; P = .819), but significantly increased the frequency of febrile neutropenia and sepsis events. While stratification of treatment intensity based on MRD was not beneficial, molecular markers of relapse risk proposed by the Japan Childrens Cancer Group for ML-DS (alterations of CDKN2A, ZBTB7A, JAK2, TP53) proved prognostic. Relapse risk was 50% in patients who were HR from AAML1531 with any high-risk molecular marker compared with 6.7% in those without. Similar relapse results were obtained in the MRD-negative AAML1531 group, suggesting molecular risk markers can predict outcome and thus be used to stratify therapy in ML-DS. This trial was registered at www.clinicaltrials.gov as #NCT02521493.

TÍTULO / TITLE: - Cancer Prevalence Among Large Cohort of Individuals With Down Syndrome: Implications for Screening Guidelines

REVISTA / JOURNAL: - Cancer Med. 2026 Jun;15(6):e72007. doi: 10.1002/cam4.72007. Free PMC article.

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AUTORES / AUTHORS: - Veronica Fitzpatrick et al.

INSTITUCIÓN / INSTITUTION: - Advocate Aurora Research Institute, Milwaukee, Wisconsin, USA.

RESUMEN / SUMMARY: - Introduction: It is known that individuals with Down syndrome (DS) have a significantly different spectrum of malignancies and neoplasms. Research shows that most solid tumors are less common among individuals with DS compared to the general population, even when adjusted for age. Conversely, individuals with DS are more likely to develop leukemia and testicular cancer. However, very little of this research has been conducted with a US-based population or on large sample sizes. Methods: This retrospective cohort study analyzed 24 years of EHR data from 5895 unique individuals with DS seen in a Midwestern US health system, with the largest designated DS clinic in the US. We calculated the point prevalence of each cancer type, based on ICD-10 coding, in our DS cohort, examined co-occurrence patterns, and compared prevalence within our sample to the US general population using SEER data from 2022. Results: Individuals with DS have significantly lower odds of cancer than the general population (OR = 0.88 (0.77-0.99)). Our cohort was 50.2% less likely to have skin cancer, 80.1% less likely to have cervical cancer, 91% less likely to have prostate cancer, and 90% less likely to have breast cancer. Zero people in our DS cohort had lung cancer. Conversely, our cohort was more likely to have leukemia and testicular cancer. Conclusion: The differences in prevalences indicate a need to consider modification of the cancer screening recommendations for people with DS and inclusion of the information in shared-decision making conversations with the patient and their family.

TÍTULO / TITLE: - Hematological Conditions in Infants With Trisomy 21

REVISTA / JOURNAL: - Neoreviews. 2026 Jan 1;27(1):e25-e38. doi: 10.1542/neo.27-1-086.

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AUTORES / AUTHORS: - Neha Bhatnagar, Irene Roberts

INSTITUCIÓN / INSTITUTION: -

RESUMEN / SUMMARY: - Virtually all neonates with Down syndrome (DS) have hematological abnormalities, including thrombocytopenia, polycythemia, and changes in the types and proportions of leukocytes. While many of these abnormalities are mild, they are important for neonatologists to be aware of, not only because some are life-threatening but also because they affect the interpretation of complete blood cell count results. The most serious hematological condition in neonates with DS is transient abnormal myelopoiesis (TAM), a neonatal leukemic syndrome unique to DS that is caused by mutations in the GATA1 transcription factor gene. In this review, we describe the spectrum of hematological conditions in neonates with DS and their implications, focusing primarily on TAM. We outline the approach to diagnosis and management of these conditions during the neonatal period and their significance for the health of these children in the short and long term. Lastly, we review the nonmalignant hematological abnormalities seen in neonates with DS, which are due to the effects of the extra 21 chromosome in the absence of GATA1 mutations.

Infectious diseases - Infecciones

TÍTULO / TITLE: - T-cell responses to primary SARS-CoV-2 vaccination in Down syndrome - From childhood to adulthood

REVISTA / JOURNAL: - Hum Vaccin Immunother. 2026 Dec 31;22(1):2670839. doi: 10.1080/21645515.2026.2670839. Epub 2026 Jun

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AUTORES / AUTHORS: - Lobke C M Hensen et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common genetic disorder worldwide and associated with high morbidity and mortality rates during the COVID-19 pandemic. For safety reasons, SARS-CoV-2 vaccine schedules and dosages were age-dependent, with children <12 years (y) receiving a lower dose than adolescents and adults. While we previously reported age-dependent antibody responses after SARS-CoV-2 vaccination in children with DS, cellular vaccine responses in this population remain insufficiently characterized. We evaluated vaccine-induced T-cell responses in children with DS following primary mRNA SARS-CoV-2 vaccination. We measured SARS-CoV-2-specific T-cell abundance (N = 40) and their interferon-gamma (IFNγ) production (N = 55) after spike antigen re-stimulation in participants aged 3-74 y. We found no significant difference in the re-activation of SARS-CoV-2-specific CD4+ T cells between adolescents (12-17 y) and adults. Children aged 5-11 y exhibited significantly lower re-activation of CD4+ T cells compared with adolescents. IFNγ production was similar across all age groups. Besides previously reported age-dependent antibody responses, these findings suggest that reduced dosing may also be associated with diminished T-cell re-activation in children with DS. Therefore, these children aged 5-11 y may benefit from receiving a booster or vaccine doses similar to those of older age groups to ensure optimal immunity and protection. Clinical trial registration: NCT05145348.

TÍTULO / TITLE: - Immune Dysregulation in Down Syndrome: Implications for Infectious Susceptibility and Vaccine Response

REVISTA / JOURNAL: - J Clin Immunol. 2026 Jul 24;46(1):86. doi: 10.1007/s10875-026-02054-6. Free PMC article.

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AUTORES / AUTHORS: - Sofia Solari-Hernandez et al.

INSTITUCIÓN / INSTITUTION: - Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.

RESUMEN / SUMMARY: - Down syndrome (DS), caused by trisomy 21, is characterized by complex immune dysregulation that increases susceptibility to infections and alters vaccine responsiveness. Gene dosage effects involving interferon receptor loci on chromosome 21 contribute to chronic type I interferon hyperactivation, sustained JAK-STAT signaling, and persistent expression of interferon-stimulated genes. This baseline inflammatory state is accompanied by quantitative and functional defects in both innate and adaptive immunity, including impaired neutrophil chemotaxis, pro-inflammatory monocyte polarization, reduced naïve T- and B-cell compartments, restricted antigen receptor diversity, diminished class-switched memory B cells, and features of accelerated immunosenescence. Clinically, these immune alterations are associated with an increased risk of severe respiratory viral infections, such as respiratory syncytial virus, influenza, and SARS-CoV-2, as well as reduced magnitude and durability of vaccine-induced immunity. Cohort studies in both pediatric and adult populations have reported higher rates of hospitalization and mortality, along with lower peak antibody titers and more rapid waning of immunity following vaccination. This review integrates molecular, cellular, and clinical evidence to define the interferon-driven immune phenotype in DS and its implications for susceptibility to infection and vaccination response. A mechanistic understanding of this immune landscape provides a framework for developing tailored preventive strategies and optimizing vaccination approaches in this vulnerable population.

TÍTULO / TITLE: - Preventing Differentiation Towards Primitive Macrophages in Stem Cells With Down Syndrome

REVISTA / JOURNAL: - Immunology. 2026 Mar;177(3):596-612. doi: 10.1111/imm.70070. Epub 2025 Nov 27. Free PMC article.

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AUTORES / AUTHORS: - Koki Harada et al.

INSTITUCIÓN / INSTITUTION: - oint Research Laboratory, Division of Integrated Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.

RESUMEN / SUMMARY: - Down syndrome (DS) is characterised by delayed brain development and intellectual disabilities. Brain macrophages originate from primitive macrophages that arise from mesodermal cells in the yolk sac and play a role in brain development. Previously, we showed a reduced number of brain macrophages in Ts1Cje foetuses, a murine model of DS. However, the mechanism underlying this reduction in Ts1Cje embryos remains unknown. First, in this study, we identified that the reduced brain macrophages in Ts1Cje foetuses were microglia. This study further reports the low production of primitive macrophages from Ts1Cje mouse embryonic stem cells (Ts1Cje-mESCs). Gene expression profiling in Ts1Cje-mESC-derived cells indicated the persistence of pluripotency, preference for endodermal differentiation, and suppression of mesodermal differentiation. Consistently, Ts1Cje-mESC-derived cells showed the disturbed expression of cytokine receptors and apoptosis, and a decreased number of primitive macrophages was confirmed in the Ts1Cje yolk sac. A human induced pluripotent stem cell line established from an individual with DS also showed lower primitive macrophage production relative to diploidized controls. Thus, our data indicate resistance to mesodermal differentiation and impaired production of primitive macrophages in DS, providing valuable insights into abnormalities in brain development associated with DS.

TÍTULO / TITLE: - The Dp16 Down syndrome mouse model does not exhibit oral interferon-gammopathy or susceptibility to oral candidiasis

REVISTA / JOURNAL: - mBio. 2026 Mar 11;17(3):e0387325. doi: 10.1128/mbio.03873-25. Epub 2026 Jan 26. Free PMC article.

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AUTORES / AUTHORS: - Ashira Lubkin et al.

INSTITUCIÓN / INSTITUTION: - Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.

RESUMEN / SUMMARY: - Down syndrome, or Trisomy 21, is associated with excessive interferon (IFN) signaling and concomitant susceptibility to both autoimmunity and immunodeficiency. One of the many clinical phenotypes observed in people with Down syndrome is increased risk for oral candidiasis. Because oral candidiasis can be caused by excessive IFN-γ signaling, we asked whether IFN-gammopathy could be playing a role in susceptibility to oral candidiasis in Down syndrome. We used the Dp16 mouse model of Down syndrome, which displays mild systemic interferonopathy, to model oral candidiasis. We found that the Dp16 model does not exhibit oral IFN-gammopathy and is not susceptible to oral candidiasis. We exposed the Dp16 mice to various inflammatory and infectious stimuli with the goal to induce enhanced local IFN-γ responses, but these did not induce oral IFN-gammopathy or promote susceptibility to oral candidiasis. We conclude that the Dp16 model is not well-suited to study oral IFN-gammopathy or oral candidiasis. Clinical studies of oral candidiasis in people with Down syndrome are warranted.IMPORTANCEDown syndrome, caused by three copies of chromosome 21, presents with different medical conditions in different people. One such condition for some people with Down syndrome is increased susceptibility to oral infection with the fungus Candida albicans. C. albicans is a normal member of the human oral microbiome, but it can also cause painful infections. Down syndrome causes an excess of inflammatory molecules called interferons (IFNs). Excessive inflammation due to one type of IFN, IFN-γ, can cause susceptibility to oral C. albicans infection in certain settings. Thus, we wanted to assess whether excessive IFNs may cause susceptibility to oral C. albicans infection in Down syndrome. We used the Dp16 mouse model of Down syndrome. We found, however, that Dp16 mice did not exhibit excessive IFN-γ oral mucosal responses and were not susceptible to oral C. albicans and thus

TÍTULO / TITLE: - Immune dysregulation in children with Down syndrome: clinical implications and emerging therapies

REVISTA / JOURNAL: - Curr Opin Rheumatol. 2026 Sep 1;38(5):305-313. doi: 10.1097/BOR.0000000000001174. Epub 2026 Jun 17.

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AUTORES / AUTHORS: - Jessica L Bloom, Indira Sriram

INSTITUCIÓN / INSTITUTION: - University of Colorado Anschutz Medical Campus, Department of Pediatrics, Section of Rheumatology, Aurora, Colorado, USA.

RESUMEN / SUMMARY: - Purpose of review: People with Down syndrome experience significant immune dysregulation, conferring elevated risk of autoimmune and inflammatory conditions. Despite the growing prevalence of adults living with Down syndrome, significant gaps remain in understanding and treating immune-mediated disease in this population. This review synthesizes current knowledge of immune dysregulation in Down syndrome, with focus on rheumatic manifestations and emerging therapeutic approaches. Recent findings: Trisomy 21 drives constitutive, global immune remodeling characterized by mixed interferon hyperactivation, hypercytokinemia, and myeloid and lymphoid subset remodeling toward an autoimmunity-prone, pro-inflammatory state. Down syndrome associated arthritis is a distinct and aggressive entity warranting recognition separate from juvenile idiopathic and rheumatoid arthritis. People with Down syndrome face elevated risk of SJIA-associated lung disease and diffuse alveolar hemorrhage. Medication tolerance is a significant consideration, including intolerance to methotrexate and diminished response to TNF inhibitors. Early clinical trials of JAK inhibitors demonstrate promising results across multiple immune-mediated manifestations, including skin disease, arthritis, and Down syndrome regression disorder. Summary: Immune dysregulation in Down syndrome is pervasive and mechanistically distinct, with interferon signaling as a central therapeutic target. Clinicians should be aware of Down syndrome specific diagnostic and management considerations, and future research should prioritize rigorous placebo-controlled trials and Down syndrome informed outcome measures.

TÍTULO / TITLE: - Interferon receptor gene dosage differentially regulates hypoxia-induced platelet activation and pulmonary hypertension in down syndrome

REVISTA / JOURNAL: - Front Immunol. 2026 May 22:17:1832057. doi: 10.3389/fimmu.2026.1832057. eCollection 2026.

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AUTORES / AUTHORS: - Janelle N Posey et al.

INSTITUCIÓN / INSTITUTION: - Section of Neonatology, Department of Pediatrics, University of Colorado Anschutz, Aurora, CO, United States

RESUMEN / SUMMARY: - Trisomy 21 (T21) results in Down syndrome (DS), a condition associated with a high prevalence of pulmonary complications. Pulmonary hypertension (PH) is a significant comorbidity in individuals with T21. Inflammation is a well-established driver of PH, and growing evidence implicates platelets as active contributors to inflammatory-mediated pulmonary vascular disease and PH. In T21, increased interferon (IFN) signaling resulting from an additional IFN receptor gene locus contributes to immune dysregulation, and interactions between platelet activation and IFN signaling may promote thromboinflammatory pathways associated with vascular disease. To determine whether platelet activation is altered in T21, we first measured platelet activation by flow cytometry in individuals with T21 and age-matched controls. We then utilized the Dp16 mouse model of down syndrome to investigate IFN-dependent mechanisms. WT, Dp16, and Dp162xIfnrs mice 7-9 weeks of age were exposed to 10% hypobaric hypoxia for 3 or 21 days or remained at Denver altitude. Platelet activation was measured by flow cytometry. Lungs were collected to measure PF4 by ELISA and lung platelets by IHC. Vascular remodeling was measured by IHC staining of muscularized small vessels. PH was measured by RSVP and RV hypertrophy (RVH). Baseline and agonist-induced platelet activation were increased in individuals with T21, as evidenced by elevated platelet P-selectin expression and activated αIIbβ3. To investigate the immunoregulatory mechanisms underlying T21-associated PH, we utilized the Dp16 mouse model of Down syndrome in a chronic hypoxia model of PH. Consistent with our human findings, baseline, agonist-induced, and hypoxia-induced P-selectin and αIIbβ3 activation were elevated in Dp16 mice compared with wild-type (WT). Circulating PF4 and soluble GPVI were elevated at baseline and PF4 was further increased in hypoxic Dp16 mice. Lung PF4 levels were also increased at baseline and further elevat

TÍTULO / TITLE: - Atopic outcomes in children with Down syndrome: a pilot sibling-matched case-control study

REVISTA / JOURNAL: - Front Pediatr. 2026 Jul 24:14:1883821. doi: 10.3389/fped.2026.1883821.Free PMC article.

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AUTORES / AUTHORS: - Nasser S Alharbi et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

RESUMEN / SUMMARY: - Introduction: Atopic conditions such as wheezing, asthma, allergic rhinitis, and eczema are frequently reported in children with Down syndrome. Many previous studies have used unpaired analyses that do not account for shared familial and environmental factors. Sibling-matched designs offer a robust approach for addressing these limitations but require appropriate paired statistical methods. This study aimed to assess the feasibility of a sibling-matched design for studying atopic outcomes in children with Down syndrome and to propose an appropriate methodological and statistical framework for future larger-scale studies. Methods: This pilot sibling-matched case-control study included 34 children with Down syndrome and their unaffected siblings (34 complete sibling pairs). Binary outcomes included wheezing, severe wheezing, physician-diagnosed asthma, allergic rhinitis, and eczema. Descriptive prevalence was reported, and paired comparisons were performed using exact McNemar testing based on discordant sibling pairs. Results: Wheezing and physician-diagnosed asthma were numerically more frequent among children with Down syndrome than among their unaffected siblings, but the differences did not reach statistical significance. Statistical comparisons were driven by discordant pairs, illustrating the importance of paired analytical approaches in sibling-matched studies. Conclusions: This pilot study demonstrates the feasibility of sibling-matched designs for evaluating atopic outcomes in children with Down syndrome and highlights the importance of paired statistical methods for binary outcomes. The findings primarily serve to propose a methodological framework for future adequately powered sibling-matched studies rather than to draw definitive etiological conclusions.

TÍTULO / TITLE: - COVID-19 vaccine uptake among individuals with Down syndrome in the Unites States

REVISTA / JOURNAL: - Vaccine. 2026 Oct 24:92:129128. doi: 10.1016/j.vaccine.2026.129128. Epub 2026 Sep 3. Free article

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AUTORES / AUTHORS: - Hui Nian et al.

INSTITUCIÓN / INSTITUTION: - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

RESUMEN / SUMMARY: - Introduction: Individuals with Down syndrome are at increased risk for severe disease from acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, making them a priority group for COVID-19 vaccination. Data on vaccine uptake and factors associated with vaccination are needed to inform strategies to improve uptake in this vulnerable population. Objective: To evaluate COVID-19 vaccine uptake and identify factors associated with vaccination among individuals with Down syndrome. Methods: The population included individuals with Down syndrome born during 1995-2021 and enrolled in the Tennessee Medicaid Program during the COVID-19 pandemic. We limited the study population to individuals who sought care at the Vanderbilt University Medical Center at least once between six months after their initial eligibility for the COVID-19 vaccine and October 1, 2024. Date and type of COVID-19 vaccine receipt were ascertained from the Tennessee Immunization Information System. Demographic and clinical characteristics associated with COVID-19 vaccine uptake and completion of the primary series were analyzed using multivariable logistic regression. Results: Among 438 individuals with Down syndrome, 95 (22%), 88 (20%), 187 (43%), and 68 (16%) first became eligible for COVID-19 vaccine at age 16+, 12-15, 5-11, and 6 months-4 years of age, respectively. Overall, 152 (35%) received at least one dose of the COVID-19 vaccine; of these, 138 (91%) completed the primary series. Younger age and lack of influenza vaccination history-either never or during the pandemic-were strongly associated with a reduced likelihood of receiving COVID-19 vaccine or completing the primary series. Conclusions: Only one-third of individuals with Down syndrome received any COVID-19 vaccine, indicating low uptake in this high-risk population. Readily available information on individuals age and influenza vaccination history may help identify individuals at increased risk of remaining unvaccinated, thereby in

Molecular biology/Biochemistry - Biología molecular/Bioquímica

TÍTULO / TITLE: - Rethinking Creatinine in Children With Down Syndrome

REVISTA / JOURNAL: - Acta Paediatr. 2026 Sep;115(9):1829-1830. doi: 10.1111/apa.70642. Epub 2026 Jun 18. Free PMC articl

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AUTORES / AUTHORS: - Guido Filler

INSTITUCIÓN / INSTITUTION: - Department of Paediatrics, Western University, London, Ontario, Canada.

RESUMEN / SUMMARY: -

Neurobiology - Neurobiología

TÍTULO / TITLE: - Single-cell atlas of the developing Down syndrome brain cortex

REVISTA / JOURNAL: - Nat Med. 2026 Mar;32(3):1061-1072. doi: 10.1038/s41591-026-04211-1. Epub 2026 Jan 16. Free PMC artic

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AUTORES / AUTHORS: - Michael Lattke et al.

INSTITUCIÓN / INSTITUTION: - Department of Brain Sciences, Imperial College London, London, UK.

RESUMEN / SUMMARY: - Down syndrome (DS), caused by trisomy of chromosome 21, is the leading genetic cause of intellectual disability, yet the mechanisms disrupting fetal brain development remain unclear. We performed single-cell transcriptomic and chromatin accessibility profiling of approximately 250,000 cells from 15 DS and 15 control human fetal cortices (10-20 weeks postconception). Our analysis revealed a subtype-specific reduction in RORB- and FOXP1-expressing excitatory neurons and widespread disruption of neurodevelopmental transcriptional programs. Chromosome 21 transcription factors BACH1, PKNOX1 and GABPA emerged as dosage-sensitive hubs regulating genes linked to intellectual disability. Antisense oligonucleotide-mediated normalization of these transcription factors in human neural progenitors in vitro partially rescued target gene expression. Benchmarking a humanized in vivo model captured additional molecular and cellular signatures of DS, complementing the in vitro model. Together, we present a resource defining the gene-regulatory landscape underlying cortical development in DS and highlight molecular pathways for further investigation.

TÍTULO / TITLE: - A single-cell multiomic analysis identifies molecular and gene-regulatory mechanisms dysregulated in developing Down syndrome neocortex

REVISTA / JOURNAL: - Science. 2026 Apr 23;392(6796):eaea1259. doi: 10.1126/science.aea1259. Epub 2026 Apr 23. Free PMC ar

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AUTORES / AUTHORS: - Celine K Vuong et al.

INSTITUCIÓN / INSTITUTION: - Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common genetic cause of intellectual disability, yet the cellular and molecular mechanisms driving this developmental disorder remain unclear. In this study, we profiled human mid-gestation neocortex with snMultiomics across 26 donors. We observed a reduction in neural progenitors and corticothalamic neurons and an increase of intratelencephalic neurons, accompanied by accelerated neuronal specification. We uncovered widespread changes in gene expression, chromatin accessibility, and cell interaction networks affecting neurogenesis, specification, and maturation; and in gene-regulatory networks directing these processes, including those downstream of human chromosome 21 (HSA21)-encoded genes. We identified cell-specific molecular pathways shared with other neurodevelopmental disorders and enrichment of genome-wide association study signals in DS-altered chromatin. Together, our data revealed a cascade of molecular dysregulation outlining the earliest steps in DS, providing a foundation for future therapeutic targets.

TÍTULO / TITLE: - Mapping the molecular effects of Down syndrome in the developing brain

REVISTA / JOURNAL: - Nat Rev Neurosci. 2026 Jul;27(7):462. doi: 10.1038/s41583-026-01050-4.

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AUTORES / AUTHORS: - Katherine Whalley

INSTITUCIÓN / INSTITUTION: - Nature Reviews Neuroscience,

RESUMEN / SUMMARY: -

TÍTULO / TITLE: - Synaptic and intrinsic membrane defects disrupt early neural network dynamics in Down syndrome

REVISTA / JOURNAL: - Nat Commun. 2026 Jan 22;17(1):1287. doi: 10.1038/s41467-025-68048-x. Free PMC article.

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AUTORES / AUTHORS: - Saad B Hannan et al.

INSTITUCIÓN / INSTITUTION: - Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.

RESUMEN / SUMMARY: - Down syndrome, caused by trisomy 21, affects around six million people worldwide and features learning, memory and language deficits. However, the mechanisms underlying trisomy 21 neurophenotypes involving human cortical circuitry are unknown. By characterising developing neural network dynamics and single cell excitability profiles, from synaptic and voltage-dependent ion channel behaviour using an isogenic induced pluripotent stem cell-derived neuronal model, we show that trisomy 21 impairs the activity and development of cortical circuitry. This is caused by deficient glutamatergic synaptic connectivity and by aberrant intrinsic membrane properties involving K+ and Na+ channels culminating in spike firing defects that weaken neural network activity and disrupt the synchrony of developing neurons. We also identify transiently activated A-type K+ channels, specifically Kv4.3 channels, as a key orchestrator for Down syndrome during neurodevelopment. Overall, these excitability changes will significantly contribute towards the aberrant neurophenotypes observed later on in life.

TÍTULO / TITLE: - Abnormal neuronal and synaptic morphology in Down syndrome brains reproduces in human isogenic cellular models

REVISTA / JOURNAL: - Cell Death Dis. 2026 Jun 10;17(1):730. doi: 10.1038/s41419-026-08956-y. Free PMC article.

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AUTORES / AUTHORS: - Ante Plecash et al.

INSTITUCIÓN / INSTITUTION: - Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common autosomal aneuploidy compatible with postnatal survival and is caused by full or partial trisomy of chromosome 21. In this study, human isogenic induced pluripotent stem cells (iPSCs) were differentiated into 2D neurons and cortico-striatal assembloids (hCSAs). Abnormal neuronal morphology was observed: trisomic (T21) neurons formed aggregates of cell bodies interconnected with thick neurite bundles radiating outwards, connected and overlapped with other neurons in between the bundles while disomic (D21) neurons were evenly distributed across the surface and formed strong neuronal networks. Detailed analysis revealed significantly shorter neurites with larger diameter, fewer branches, and fewer terminal points in T21 neurons compared to D21 neurons in both 2D cultures and hCSAs. We observed similar phenotypes in foetal and postnatal human brain tissue. Furthermore, we observed abnormal mitochondrial morphology with an excess of some mitochondrial proteins (AIF, TOMM20), abnormal synaptic morphology and significantly lower expression of both presynaptic and postsynaptic markers (SYN-1, PSD95 and GEPH) throughout in vitro differentiation of T21 neurons. Finally, our data showed that T21 spheroids were significantly smaller throughout in vitro differentiation compared to D21 spheroids. T21 spheroids also exhibited significantly higher expression of neural stem cells (SOX2), significantly lower expression of proliferating cells (Ki67) and significantly higher expression of apoptotic cells (CCaspase-3). Overall, our study demonstrates that T21 leads to abnormal neuronal morphology in both 2D neurons and hCSAs, consistent with observations in the human brain.

TÍTULO / TITLE: - REST deficiency and neurogenic-to-gliogenic shift in down syndrome human cerebral organoids

REVISTA / JOURNAL: - Mol Brain. 2026 May 16;19(1):55. doi: 10.1186/s13041-026-01313-2. Free PMC article.

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AUTORES / AUTHORS: - Tan Huang et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi City, 563000, Guizhou Province, China.

RESUMEN / SUMMARY: - Down syndrome (DS) features impaired cortical neurogenesis and excess gliogenesis, yet the temporal regulatory events driving this imbalance remain unclear. Here, we combine multi-timepoint transcriptomic analyses from publicly available datasets, network modelling, and machine-learning prioritization, with validation in isogenic human iPSC-derived cerebral organoids, to identify a discrete pathogenic window at 90 days in vitro (DIV 90). Across five developmental stages, REST target genes were preferentially dysregulated in DS organoids. WGCNA revealed a DS-associated module at DIV-90 that strongly overlapped with REST targets, and two orthogonal machine-learning approaches converged on six REST-regulated hub genes-CSTB, MCM3AP, PFKL, POFUT2, PRMT2, and RWDD2B. In trisomic organoids, REST mRNA and nuclear protein were markedly reduced at DIV-90, accompanied by diminished DCX expression and activation of NFIA and STAT3, suggesting a neurogenic-to-gliogenic fate transition. These findings suggest REST dysfunction as a potential temporal regulator of lineage imbalance in DS and highlight REST-linked networks as potential targets for early developmental intervention.

Neurology - Neurología

TÍTULO / TITLE: - Natural history and clinical impact of epilepsy in adults with Down syndrome: a multicentre clinical study

REVISTA / JOURNAL: - Lancet. 2026 Sep 26;408(10561):1198-1210. doi: 10.1016/S0140-6736(26)00980-3. EFree article

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AUTORES / AUTHORS: - Lucia Maure-Blesa et al.

INSTITUCIÓN / INSTITUTION: - Sant Pau Memory Unit, IR SANT PAU, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain.

RESUMEN / SUMMARY: - Background: As individuals with Down syndrome age, they face high risks of Alzheimers disease and epilepsy. With symptomatic Alzheimers disease, late-onset myoclonic epilepsy in Down syndrome (LOMEDS) often emerges. We aimed to examine how epilepsy develops in Down syndrome, its timing relative to Alzheimers disease symptom onset, and its effect on prognosis. Methods: We conducted a multicentre, observational, longitudinal study across seven international cohorts with an aggregate observation window from Oct 24, 2012, to July 28, 2025. We included adults with Down syndrome aged at least 18 years and with at least one longitudinal clinical assessment. Alzheimers disease staging was done by clinical consensus. Active epilepsy required an epilepsy diagnosis plus ongoing antiseizure medication or at least one seizure within the past 5 years. We analysed active epilepsy prevalence, incidence and cumulative incidence, its timing with respect to symptomatic Alzheimers disease, and its effect on survival and cognitive trajectories as well as electroencephalogram (EEG) abnormalities. Findings: We included 4804 adults with Down syndrome (mean age 43 years [SD 13]): 3238 (67·4%) were cognitively stable, 267 (5·6%) had non-degenerative cognitive decline, 321 (6·7%) had prodromal Alzheimers disease, and 978 (20·3%) had Alzheimers disease dementia. Intellectual disability was mild in 1020 (24·6%) participants, moderate in 2352 (56·7%), and severe to profound in 779 (18·8%). Active epilepsy prevalence was 145·2 per adults with Down syndrome overall but significantly increased with age, particularly with symptomatic Alzheimers disease, when epilepsy manifested mostly as myoclonic or tonic-clonic seizures. Cumulative incidence of epilepsy increased linearly after symptomatic Alzheimers disease, from 9·5% (95% CI 7·8-11·3) at diagnosis to 56·9% (51·7-61·7) after 9 years. Risk of epilepsy increased with time since Alzheimers disease diagnosis (adjusted odds ratio 1·33 per year [95% C

TÍTULO / TITLE: - Natural history and clinical impact of epilepsy in adults with Down syndrome: a multicentre clinical study

REVISTA / JOURNAL: - Lancet. 2026 Sep 26;408(10561):1198-1210. doi: 10.1016/S0140-6736(26)00980-3. EFree article

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AUTORES / AUTHORS: - Lucia Maure-Blesa et al.

INSTITUCIÓN / INSTITUTION: - Sant Pau Memory Unit, IR SANT PAU, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain.

RESUMEN / SUMMARY: - **Background:** As individuals with Down syndrome age, they face high risks of Alzheimers disease and epilepsy. With symptomatic Alzheimers disease, late-onset myoclonic epilepsy in Down syndrome (LOMEDS) often emerges. We aimed to examine how epilepsy develops in Down syndrome, its timing relative to Alzheimers disease symptom onset, and its effect on prognosis. **Methods:** We conducted a multicentre, observational, longitudinal study across seven international cohorts with an aggregate observation window from Oct 24, 2012, to July 28, 2025. We included adults with Down syndrome aged at least 18 years and with at least one longitudinal clinical assessment. Alzheimers disease staging was done by clinical consensus. Active epilepsy required an epilepsy diagnosis plus ongoing antiseizure medication or at least one seizure within the past 5 years. We analysed active epilepsy prevalence, incidence and cumulative incidence, its timing with respect to symptomatic Alzheimers disease, and its effect on survival and cognitive trajectories as well as electroencephalogram (EEG) abnormalities. **Findings:** We included 4804 adults with Down syndrome (mean age 43 years [SD 13]): 3238 (67.4%) were cognitively stable, 267 (5.6%) had non-degenerative cognitive decline, 321 (6.7%) had prodromal Alzheimers disease, and 978 (20.3%) had Alzheimers disease dementia. Intellectual disability was mild in 1020 (24.6%) participants, moderate in 2352 (56.7%), and severe to profound in 779 (18.8%). Active epilepsy prevalence was 145.2 per adults with Down syndrome overall but significantly increased with age, particularly with symptomatic Alzheimers disease, when epilepsy manifested mostly as myoclonic or tonic-clonic seizures. Cumulative incidence of epilepsy increased linearly after symptomatic Alzheimers disease, from 9.5% (95% CI 7.8-11.3) at diagnosis to 56.9% (51.7-61.7) after 9 years. Risk of epilepsy increased with time since Alzheimers disease diagnosis (adjusted odds ratio 1.3

Ophtalmology - Oftalmología

TÍTULO / TITLE: - Ophthalmic screening in down syndrome: A DSMIG UK Best practice recommendation (Revised 2025)

REVISTA / JOURNAL: - Eye (Lond). 2026 Apr;40(5):569-571. doi: 10.1038/s41433-026-04310-w. Epub 2026 Feb 20.

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AUTORES / AUTHORS: - George Riding et al. Down Syndrome Medical Interest Group (DSMIG) UK

INSTITUCIÓN / INSTITUTION: - Royal Free Hospital, Pond St, London, NW3 2QG, UK

RESUMEN / SUMMARY: -

Physiotherapy/Exercise – Fisioterapia/Ejercicio

TÍTULO / TITLE: - Effectiveness of Resistance Training in People With Down Syndrome: Systematic Review and Meta-Analysis

REVISTA / JOURNAL: - J Appl Res Intellect Disabil. 2026 Sep;39(5):e70302. doi: 10.1111/jar.70302. Free PMC article.

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AUTORES / AUTHORS: - Maria Jesus Benzo Iglesias et al.

INSTITUCIÓN / INSTITUTION: - Health Research Centre, Humanidades-498 Research Group, Department of Nursing, Physiotherapy and Medicine, University of Almeria, Almeria, Spain.

RESUMEN / SUMMARY: - Background: We aimed to evaluate the effectiveness of resistance training (RT) in people with Down syndrome (DS) as a way of improving strength, physical and metabolic function, and possible adverse effects. Methods: Systematic review and meta-analysis of RCTs in PubMed, PEDro, Scopus, and WoS databases in September-2023, registered in PROSPERO (CRD42022312810). Methodological quality and risk of bias were analysed using the PEDro scale, the Downs & Black Checklist, and the Cochrane Collaboration Risk of Bias Tool. Results: Sixteen articles were included. RT increased the strength (SMD = 1.88; 95% CI = (1.26; 2.51); I2 = 72%) and improved physical function (SMD = -0.58; 95% CI = (-1.06; -0.11); I2 = 13%), but there were no clear results on whether it improved anthropometric and cardiorespiratory measures. There were no serious adverse effects. Conclusion: An increase in overall and maximal muscle strength and improved physical function was produced by RT in DS people. RT is a safe technique as serious adverse effects were not produced.

Prenatal diagnosis - Diagnóstico

TÍTULO / TITLE: - Impact of National Screening Programs on Down syndrome prevalence and outcomes

REVISTA / JOURNAL: - Acta Obstet Gynecol Scand. 2026 Apr;105(4):613-620. doi: 10.1111/aogs.70157. Epub 2026 Feb 13. Free

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AUTORES / AUTHORS: - Cecilie Bryn Nordklev et al

INSTITUCIÓN / INSTITUTION: - Fetal Medicine Centre, Oslo University Hospital, Oslo, Norway

RESUMEN / SUMMARY: - Introduction: Over the past five decades, antenatal screening programs have evolved significantly, primarily through advancements in ultrasound technology and the shift from invasive to non-invasive prenatal testing methods. This study aimed to evaluate the impact of these developments in prenatal screening for Down syndrome (DS) on the prevalence of live and stillbirths, as well as terminations of pregnancy (TOP) with DS. Material and methods: This population-based registry study included all pregnancies in Norway from 1967 to 2021, with data on TOPs available from 1999. Information on DS pregnancies was obtained from the Medical Birth Registry of Norway. Logistic regression models were applied to evaluate time trends and maternal characteristics associated with TOP. Results: Among 3 231 159 pregnancies, 4764 (0.147%) were affected by DS. The prevalence of DS pregnancies increased from 0.165% in 1999 to 0.251% in 2021. During this period, the proportion of TOP rose from 20% to 55%, while prenatal detection rates improved from 18% to 70%. Despite increased detection, the proportion of TOP following prenatal diagnosis remained stable at approximately 80%. The prevalence of live births with DS remained stable at approximately 0.106%, while the prevalence of stillbirths was around 0.008%. Maternal age, parity, country of birth, and region of residence were associated with TOP decisions. Mean gestational age at termination decreased from 17.5 to 15.7 weeks. Conclusions: Over recent decades, prenatal detection and termination of DS pregnancies have increased. However, the proportion of women continuing pregnancies after a prenatal diagnosis and the prevalence of live- and stillbirths with DS have remained stable.

Psychiatry - Psiquiatría

TÍTULO / TITLE: - Caregiver Perceived Barriers to Diagnosis and Care in Down Syndrome Regression Disorder

REVISTA / JOURNAL: - Am J Med Genet A. 2026 Feb;200(2):379-406. doi: 10.1002/ajmg.a.64274. Epub 2025 Oct 8.

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AUTORES / AUTHORS: - Anya Alag et al.

INSTITUCIÓN / INSTITUTION: - Division of Neurology, Department of Pediatrics, Childrens Hospital Los Angeles, Los Angeles, California, USA.

RESUMEN / SUMMARY: - Down Syndrome Regression Disorder (DSRD) is a rare neuropsychiatric condition affecting individuals with Trisomy 21. Barriers to care for DSRD patients have not been studied. This research aimed to explore how demographic, socioeconomic, and geographic factors influence access to diagnosis, testing, and treatment for individuals with DSRD. A cross-sectional, online, REDCap survey was utilized to query caregivers of individuals with DSRD. Eligible caregivers answered questions regarding demographics, clinical features, and barriers to diagnosis and treatment. Statistical analysis was performed using R software, employing χ 2, Mann-Whitney U, and Kruskal-Wallis H tests. A total of 397 participants were enrolled, most from the US (74%). Barriers to diagnosis (58.1%), treatment (52.6%), referral (52.0%), and testing (39.4%) were prevalent. Key barriers included physician unfamiliarity with DSRD and a lack of local specialists. Travel distances for diagnosis, testing, and treatment were significant, with 14.7% traveling over 500 miles for diagnosis and some requiring international travel. Factors influencing delays in diagnosis and treatment included household income, region, and demographic variables. Higher income was associated with shorter time to diagnosis (p = 0.004) and treatment (p < 0.001). Race, income, maternal education, and setting influenced delays in diagnosis. Delays in treatment were influenced by ethnicity, income, and location. This large international survey of caregivers of individuals with DSRD elucidates perceived barriers to accessing diagnosis, testing, and treatment, with demographic factors such as socioeconomic status and geography influencing these challenges. The directionality of these effects and their impact on clinical care and outcomes will be a logical basis for additional studies. Further studies are needed to explore these barriers in greater depth and assess their impact on healthcare outcomes.

TÍTULO / TITLE: - Age Differences in Emotion Regulation Among Individuals With Down Syndrome

REVISTA / JOURNAL: - J Intellect Disabil Res. 2026 Aug 24. doi: 10.1111/jir.70163. Online ahead of print.

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AUTORES / AUTHORS: - Sophie Kowalski, Caron A C Clark

INSTITUCIÓN / INSTITUTION: - Department of Educational Psychology, University of Nebraska, Lincoln, United States

RESUMEN / SUMMARY: - Background: Although there is clear evidence that individuals with Down syndrome (DS) experience difficulties in identifying and interpreting emotions, there is limited research on emotional regulation in this population. Furthermore, many studies of individuals with DS focus on group comparisons against typically developing children, with few considering the role of development itself. Here, we addressed these gaps in the literature by examining individual differences in emotion regulation among individuals with DS using a multi-measure, multi-informant approach. Method: Thirty-eight individuals with DS aged 5-47 years and their caregivers completed an emotion recognition task, direct observations of their emotional negativity and self-comforting strategies during a frustrating puzzle and caregiver and participant reports of emotion regulation. Participants language and executive function skills were also assessed. Results: Higher age was linked to less negativity and reduced use of comfort strategies during the puzzle task, although the relation of age to negativity was curvilinear, with negative behaviours being more prevalent again in late adulthood. Caregiver and self-reports indicated lower emotional lability among older participants. Language scores were linked to emotion recognition and caregiver-reported emotion regulation. Although correlated themselves, emotion recognition and executive function did not correlate significantly with other emotional regulation measures. Conclusion: Although further longitudinal research is required, results highlight the importance of a developmental perspective in research on emotion regulation in this population and suggest that interventions to enhance emotion regulation strategies may best be tailored to younger individuals with DS, whereas interventions that target language and executive function may support emotion recognition regardless of age.

Quality of life - Calidad de vida

TÍTULO / TITLE: - Not Just a Pediatric Condition: Down Syndrome Across the Lifespan

REVISTA / JOURNAL: - Mo Med. 2026 Jul-Aug;123(4):327-330. Free PMC article.

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AUTORES / AUTHORS: - Emily Haury et al

INSTITUCIÓN / INSTITUTION: - Associate Professor of Internal Medicine/Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.

RESUMEN / SUMMARY: - With increasing life expectancy for individuals with Down Syndrome (DS), there are growing numbers of adult DS patients needing care from primary care physicians who are knowledgeable regarding their health needs and risks. The Global Down Syndrome Foundation (GDSF) Medical Care Guidelines for Adults with Down Syndrome identify important areas of focus: mental health, dementia, diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, hypothyroidism and celiac disease. Additionally, there are unique considerations regarding cancer risk and screenings, as well as vaccination. Young adults with DS should have a structured transition from pediatric to adult care like any patient with chronic illness or intellectual disability. This article highlights several organizations and programs that provide social, vocational, legal, and family support for Missouri patients with Down Syndrome.

TÍTULO / TITLE: - Stories about self-perceived quality of life from adults with Down syndrome

REVISTA / JOURNAL: - J Intellect Disabil. 2026 Aug 21:17446295261479795. doi: 10.1177/17446295261479795. Online ahead of

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AUTORES / AUTHORS: - Catharina Pedersen, Roald Undlien

INSTITUCIÓN / INSTITUTION: - Faculty of Social and Health Sciences, University of Inland Norway, Lillehammer, Norway.

RESUMEN / SUMMARY: - This study explores the self-perceived quality of life among five adults with Down syndrome in Norway. Data were collected through qualitative semi-structured interviews with five adults with Down syndrome, supplemented by the Personal Wellbeing Index - Intellectual Disability, and analysed using reflexive thematic analysis. The findings highlight four themes contributing to their quality of life: (1) Adulthood, autonomy and independence, (2) Health experiences, self-care, and navigating barriers, (3) Pursuing dreams and ambitions, and finding joy in daily life, (4) Freedom and leisure: personal choices. These five participants narratives provide rich insights into their lived experiences, emphasizing the importance of supporting their autonomy and independence. These findings suggest that tailored support systems are crucial for enhancing the quality of life for adults with Down syndrome. Further research is needed to explore these aspects in larger and more diverse samples.

Respiratory - Respiratorio

TÍTULO / TITLE: - Interferon receptor gene dosage differentially regulates hypoxia-induced platelet activation and pulmonary hypertension in down syndrome

REVISTA / JOURNAL: - Front Immunol. 2026 May 22:17:1832057. doi: 10.3389/fimmu.2026.1832057. eCollection 2026.

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AUTORES / AUTHORS: - Janelle N Posey et al.

INSTITUCIÓN / INSTITUTION: - Section of Neonatology, Department of Pediatrics, University of Colorado Anschutz, Aurora, CO, United States

RESUMEN / SUMMARY: - Trisomy 21 (T21) results in Down syndrome (DS), a condition associated with a high prevalence of pulmonary complications. Pulmonary hypertension (PH) is a significant comorbidity in individuals with T21. Inflammation is a well-established driver of PH, and growing evidence implicates platelets as active contributors to inflammatory-mediated pulmonary vascular disease and PH. In T21, increased interferon (IFN) signaling resulting from an additional IFN receptor gene locus contributes to immune dysregulation, and interactions between platelet activation and IFN signaling may promote thromboinflammatory pathways associated with vascular disease. To determine whether platelet activation is altered in T21, we first measured platelet activation by flow cytometry in individuals with T21 and age-matched controls. We then utilized the Dp16 mouse model of down syndrome to investigate IFN-dependent mechanisms. WT, Dp16, and Dp162xIfnrs mice 7-9 weeks of age were exposed to 10% hypobaric hypoxia for 3 or 21 days or remained at Denver altitude. Platelet activation was measured by flow cytometry. Lungs were collected to measure PF4 by ELISA and lung platelets by IHC. Vascular remodeling was measured by IHC staining of muscularized small vessels. PH was measured by RSVP and RV hypertrophy (RVH). Baseline and agonist-induced platelet activation were increased in individuals with T21, as evidenced by elevated platelet P-selectin expression and activated αIIbβ3. To investigate the immunoregulatory mechanisms underlying T21-associated PH, we utilized the Dp16 mouse model of Down syndrome in a chronic hypoxia model of PH. Consistent with our human findings, baseline, agonist-induced, and hypoxia-induced P-selectin and αIIbβ3 activation were elevated in Dp16 mice compared with wild-type (WT). Circulating PF4 and soluble GPVI were elevated at baseline and PF4 was further increased in hypoxic Dp16 mice. Lung PF4 levels were also increased at baseline and further elevat

Education - Educación

TÍTULO / TITLE: - Occupational Therapy Interventions in Down Syndrome: A Scoping Review

REVISTA / JOURNAL: - Am J Occup Ther. 2026 Sep-Oct;80(5):898-907. doi: 10.1177/19437676261464084. Epub 2026 Jul 19.

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AUTORES / AUTHORS: - Katherine L Long et al.

INSTITUCIÓN / INSTITUTION: - Department of Psychology, Florida International University, Miami, FL, USA.

RESUMEN / SUMMARY: - Importance Individuals with Down syndrome experience multiple conditions requiring occupational therapy intervention, but no review papers have explored the research literature to support such intervention.ObjectiveTo map the literature on occupational therapy interventions for individuals with Down syndrome across the lifespan and identify gaps in the evidence base for future research and education that require attention.Data SourcesSix databases were searched: OTSeeker, PubMed, PsychINFO, PEDro, CINAHL, and Cochrane Library for studies published on or before June 19, 2025.Study Selection and Data CollectionThis review was conducted according to PRISMA-ScR and Joanna Briggs Institute methodology for scoping reviews. Included studies had participants with Down syndrome, were published in English, contained an OT intervention, and were peer-reviewed. Excluded studies lacked participants with Down syndrome, were not in English, did not have an OT intervention, or were not peer-reviewed.FindingsWe retrieved 421 records and included 21 articles in this review. While most studies utilized rigorous designs (n = 16), none were designated "High Quality" due to multiple methodological flaws, such as failure to assess treatment fidelity or lack of random assignment to condition.Conclusions and RelevanceThis review suggests a need for studies with more methodological rigor, that address adults with Down syndrome, and that detail a greater variety of interventions. Practitioners and scholars should emphasize data-driven decision making, implementation of practice guidelines for Down syndrome, and the promotion of continuing education opportunities on Down syndrome.

TÍTULO / TITLE: - Cognitive Predictors of Adaptive Behaviour in Children With Down Syndrome: A Systematic Review

REVISTA / JOURNAL: - J Appl Res Intellect Disabil. 2026 Jan;39(1):e70201. doi: 10.1111/jar.70201. Free PMC article.

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AUTORES / AUTHORS: - Fernanda Silva Pereira et al.

INSTITUCIÓN / INSTITUTION: - Graduate Program in Child and Adolescent Health in Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.

RESUMEN / SUMMARY: - Background: Children with Down Syndrome, caused by trisomy 21, frequently exhibit deficits in adaptive behaviour. This systematic review aimed to identify predictors of adaptive behaviour in children with Down Syndrome. Method: The review followed PRISMA guidelines and was registered in PROSPERO (CRD420251071028). Searches were conducted in June 2025 in PsycINFO, Scopus, ERIC, Web of Science and PubMed. Results: A total of 257 articles were yielded, of which eight met the eligibility criteria. Across studies, executive functions consistently stood out as the strongest predictors of adaptive behaviour, explaining variance in communication, socialisation and daily living skills. General cognitive skills were also associated, although with smaller effects. Conclusions: Overall, these findings highlight that deficits in executive and intellectual functioning constrain autonomy and everyday functioning in Down Syndrome, underscoring the importance of targeted interventions to improve adaptive outcomes.

TÍTULO / TITLE: - Comparative language performance in children and adolescents with 22q11.2ds syndrome and down syndrome

REVISTA / JOURNAL: - J Neurodev Disord. 2026 May 26;18(1):44. doi: 10.1186/s11689-026-09701-4. Free PMC article.

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AUTORES / AUTHORS: - Esther Moraleda-Sepulveda et al.

INSTITUCIÓN / INSTITUTION: - Department of Psychology, Faculty of Pychology, University Complutense, Campus de Somosaguas, 28223, Pozuelo de Alarcon, Madrid, Spain.

RESUMEN / SUMMARY: - Genetically defined neurodevelopmental syndromes provide a framework for examining constraints on language development. This study compared language performance in children and adolescents with 22q11.2 deletion syndrome (22q11.2DS; n = 40) and Down syndrome (DS; n = 40), matched for age and nonverbal cognitive ability, aged 6-16 years. Standardized assessments included the Clinical Evaluation of Language Fundamentals (CELF-5) and the BLOC-C to evaluate multiple receptive and expressive language domains. Group differences, effect sizes, and associations with age were analyzed to characterize syndrome-specific profiles. Children with 22q11.2DS demonstrated relatively stronger receptive vocabulary and syntax alongside weaker morphosyntactic and pragmatic skills, with vocabulary showing moderate positive associations with age. In contrast, the DS group exhibited generally lower performance across domains, with pronounced difficulties in morphosyntax and limited age-related gains. These findings highlight differences in overall level of performance and relative strengths within a globally impaired profile across syndromes and emphasize the value of multi-dimensional assessment in capturing both age-related patterns and vulnerabilities.

TÍTULO / TITLE: - Developmental Profile and Variability in Preschool-Age Children With Down Syndrome

REVISTA / JOURNAL: - J Intellect Disabil Res. 2026 Aug;70(8):881-886. doi: 10.1111/jir.70126.Epub 2026 Jun 2.Free PMC art

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AUTORES / AUTHORS: - Sara Onnivello et al.

INSTITUCIÓN / INSTITUTION: - Department of Developmental Psychology and Socialization, University of Padova, Padova, Italy.

RESUMEN / SUMMARY: - Background: The developmental and cognitive profile of Down syndrome (DS) has been studied across various age groups, but we have still a limited understanding of the preschool-age range, including the domains that show the greatest variability at this age. Our study aims to (1) define the developmental profile in preschool-age children with DS and (2) explore variability within domains of functioning. Method: We assessed 43 preschool-aged children with DS (38-76 months) using the Griffiths-III scales. This tool assesses development across five scales: Foundations of Learning, Language and Communication, Eye and Hand Coordination, Personal-Social-Emotional and Gross Motor Skills. We employed multivariate linear models for analysis. Results: The analyses revealed a peaks-and-valleys profile, with higher scores in the Personal-Social-Emotional and Gross Motor domains compared to the Foundations of Learning, Language and Communication and Eye and Hand Coordination scales. Notably, high interindividual variability was observed in the Language and Communication and Personal-Social-Emotional domains. Conclusions: Our findings identify strengths and weaknesses in specific domains within the preschool-aged range and show higher variability in the verbal and personal-social-emotional domains. All this information offers valuable insights for early intervention planning, supporting parents, caregivers, and stakeholders in promoting optimal development in children with DS.