Down syndrome and intellectual disability research

Reduced cerebral blood flow and metabolic rate trigger an adaptive mitochondrial remodeling program in a Down syndrome mouse model

In Dp16 Down syndrome mice, MRI shows reduced cerebral blood flow and oxygen metabolism (significant in males), while brain mitochondrial respiratory capacity stays largely intact and oxidative phosphorylation genes rise.

Elevated mitochondrial metabolism in Down syndrome iPSCs reduces commitment to neuroectoderm

This study shows that increased mitochondrial metabolism in Down syndrome iPSCs impairs neuroectoderm commitment by reducing ciliation, and this effect can be reversed by inhibiting mitochondrial calcium uptake.

Responses to unannounced rule changes in adults with developmental disabilities: A community-based pilot study with consumer-grade EEG

This study uses EEG to examine how adults with developmental disabilities respond to unannounced rule changes, finding individual differences in error patterns and brain activity related to adapting to change.

A Trisomy 21 Model Atlas reveals conserved dosage effects and context-specific transcriptional responses across mouse and human models of Down syndrome

The paper presents a Trisomy 21 Model Atlas comparing mouse and human models to show conserved dosage effects and context-specific transcriptional responses across tissues and developmental stages.

Common cis-eQTLs do not explain chromosome 21 expression deviations from the ploidy expectation in Down syndrome

The paper investigates whether common cis-eQTLs explain gene expression deviations from ploidy expectations in Down syndrome using transcriptomic data from the Human Trisome Project and GTEx.

HDAC inhibitor treatment restores transcriptome, chromatin accessibility and memory deficits in a mouse model for Down syndrome

Obesity-related alterations in plasma metabolomics and fecal microbiota in Down syndrome Dp(16)1Yey mice

The paper examines how diet and genetic factors affect metabolomics and microbiota in a Down syndrome mouse model, identifying interactions that influence metabolic pathways.

Sequence and epigenetic characterization of chromosome 21 centromeres in a family with recurrent Trisomy 21

The paper characterizes chromosome 21 centromeres in a family with recurrent Trisomy 21, identifying a diffuse hypomethylation pattern linked to maternal age-related risk.

Deep phenotyping and multi-omics analyses reveal systems-wide metabolic dysregulation in a refined trisomy mouse model of Down syndrome

The paper compares metabolic dysregulation in two Down syndrome mouse models, finding Ts66Yah exhibits more severe metabolic disturbances than Ts65Dn.

Cellular Morphology and Motility Defects are Conserved Phenotypes of Trisomy 21 Despite Heterogeneous Adhesion Mechanisms

This study shows that cellular morphology and motility defects are consistent in Down syndrome across different cell types, despite variable adhesion mechanism changes.

Oligodendrocyte Enriched Brain Organoids Reveal Impaired Oligodendroglial Maturation and Altered Neural Network Activity in Down Syndrome

This study uses brain organoids to show trisomy 21 impairs oligodendrocyte maturation and neural network function in Down syndrome.

Identification of the Down syndrome critical region 3 gene as a mammalian cell size regulator

This study identifies DSCR3 as a gene that regulates cell size, showing its overexpression increases cell size and its knockdown reduces it in fibroblasts.

Altered follicular immunity in secondary lymphoid organs is associated with interferon hyperactivity in Down syndrome

This study identifies altered follicular immunity and interferon hyperactivity in Down syndrome through single-cell and spatial profiling of human tonsils.

Progressive deterioration of adaptive immune repertoires in Down syndrome linked to interferon hyperactivity and lymphoid tissue disorganization

This study identifies hyperactive interferon signaling and lymphoid tissue disorganization as drivers of adaptive immune dysfunction in Down syndrome across development and aging.

Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model

Dp16 mice, carrying 115 triplicated Hsa21 orthologs, show sex-shared insulin resistance, glucose intolerance and dyslipidemia, worsened by high-fat diet, with multi-tissue transcriptome and metabolome signatures.

Sex-specific developmental phenotypes and their response to neonatal Dyrk1a reduction in the Ts65Dn Down syndrome mouse model

This study examines sex-specific developmental effects of neonatal Dyrk1a reduction in Ts65Dn Down syndrome mice, finding partial improvements in some phenotypes but not all.

Extracellular matrix defects destabilise apical cytoarchitecture and mechanical properties during early Down syndrome neurodevelopment

This study shows that ECM defects in Down syndrome neurodevelopment cause apical cytoarchitecture and mechanical property instability in neural stem cell models.

Variation in infant subcortical brain development from 6 to 12 months in Down syndrome

This study examines subcortical brain development in infants with Down syndrome compared to controls from 6 to 12 months, finding reduced volumes and slower growth in most structures.

Complete chromosome 21 centromere sequencing of families with Down syndrome reveals centromere size asymmetry

The paper sequences chromosome 21 centromeres in Down syndrome families, finding extreme size asymmetry in some cases and suggesting it may be a genetic risk factor.

Abnormal neuronal and synaptic morphology in Down syndrome brains reproduces in human isogenic cellular models

This study shows that trisomy 21 in human isogenic iPSC-derived neurons leads to abnormal neuronal and synaptic morphology, similar to findings in human brain tissue.

LONG-TERM NEURODEVELOPMENTAL AND COGNITIVE OUTCOMES FOLLOWING PRENATAL INHIBITION OF DYRK1A BY LEUCETTINE L41 IN MOUSE MODELS OF DOWN SYNDROME

This study investigates the effects of prenatal DYRK1A inhibition with Leucettine L41 in DS mouse models, showing lasting cognitive and gene expression improvements with model-specific outcomes.

Differential efficacy of α5IA in the Dp(16)1Yey mouse model of Down syndrome: implications for translational research

This study evaluates the efficacy of 5IA in the Dp(16)1Yey mouse model of Down syndrome, finding improved motor coordination but no cognitive rescue, suggesting divergent pathophysiology compared to Ts65Dn models.

A single cell multi-omic analysis identifies molecular and gene-regulatory mechanisms dysregulated in the developing Down syndrome neocortex

This study uses single-nucleus multi-omics to analyze the developing Down syndrome neocortex, identifying dysregulated molecular and gene-regulatory mechanisms affecting neurogenesis and cell specification.

Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex

This study uses single-nucleus multiomic sequencing to analyze gene expression and chromatin accessibility in the Down syndrome prefrontal cortex, revealing widespread dysregulation in metabolic, synaptic, and neuroinflammatory pathways.

Epigenetically constrained astrocyte states underlie prefrontal cortex vulnerability in Down syndrome associated Alzheimer disease

The paper identifies a vulnerable astrocyte state in the prefrontal cortex of Down syndrome-associated Alzheimer's disease through integrated single-nucleus RNA-seq and ATAC-seq analysis.

Anti-inflammatory and pro-proliferative effects of fasudil in human trisomy 21 neural progenitor cells

This study evaluates fasudil's effects on trisomy 21 neural progenitor cells, showing increased proliferation and reduced inflammation.

Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B

Genetic analysis of triplicated genes affecting sex-specific skeletal deficits in Down syndrome model mice

The paper compares skeletal phenotypes between two Down syndrome mouse models, Ts65Dn and Ts66Yah, using a novel PCA-based method to assess the impact of non-Hsa21 trisomic genes on bone structure and function.

Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 iPSC-derived neural cells

This study shows that Leucettinib-21 reduces DYRK1A activity in human trisomy 21 neural cells, supporting its potential as a therapeutic for Down syndrome.

Synaptic and intrinsic membrane defects disrupt early neural network dynamics in Down syndrome

This study shows that trisomy 21 impairs cortical circuit development by disrupting synaptic connectivity and intrinsic membrane properties in neurons.