Down syndrome and intellectual disability research

The paper reports altered hepatic metabolism in Down syndrome using multi-omic analysis of plasma and mouse models, showing increased bile acids and liver dysfunction that can be modulated by diet.

This study investigates the role of APP overdose in Down Syndrome by reducing APP dosage in DS iPSCs and assessing its impact on neurogenesis and Alzheimer's disease pathology.

The paper constructs a single-cell atlas of fetal Down syndrome cortex, identifying chromosome 21 transcription factors that regulate intellectual disability gene networks and showing their normalization can restore molecular signatures.

This study identifies pleiotrophin dysregulation in astrocytes as a contributor to neuronal structural and functional deficits in Down Syndrome, showing potential for therapeutic intervention.

This study shows that reducing APP gene copy number in Down syndrome cortical organoids improves neural progenitor cell proliferation and neuronal differentiation.

The paper investigates GABA inhibition in Down syndrome mouse models, finding circuit-specific increases in inhibition in the dentate gyrus due to gene dosage effects.

The paper uses single-nucleus sequencing to identify oxidative stress and metabolic changes in Down syndrome basal forebrain neurons at birth.

This study integrates transcriptomic and genetic data to identify molecular signatures and potential biomarkers for Down syndrome comorbidities.

This study shows that inhibiting Mediator kinases CDK8/CDK19 suppresses hyperactive IFN signaling in Down syndrome by affecting transcription, splicing, and lipid metabolism.

This study identifies CBR1 as a regulator of blood pressure in Down Syndrome, showing that its inhibition can increase blood pressure in a DS mouse model.

This study investigates immune dysregulation in Down syndrome and shows that JAK inhibition with tofacitinib reduces autoimmune symptoms and inflammatory markers without significant adverse effects.

The paper identifies DYRK1A triplication as the major cause of otitis media in Down syndrome by using mouse models and shows that normalizing its dosage restores the wild-type phenotype.

This study shows that adult choline supplementation in a Down syndrome mouse model improves cognitive flexibility, reduces weight gain, and decreases inflammation and glucose metabolism issues.

This study identifies Ripply3 overdosage as a cause of mid-face shortening in Down syndrome models through Tbx1 downregulation during branchial arch development.

This study performs genome-wide association analyses of congenital heart defects in Down syndrome, identifying suggestive loci associated with specific heart defect subtypes.

This study uses a dynamic in vitro model to correct Trisomy 21 gene dosage in DS neurogenesis and shows XIST can suppress chr21 genes even after terminal differentiation.

The paper analyzes bone development and gene expression in Ts65Dn mice to identify timepoints when trisomic Dyrk1a overexpression links to skeletal abnormalities, showing sex-dependent differences in deficit timing and resolution.

The paper measures epigenetic age in Ts65Dn mice using a mouse-specific clock and finds increased hippocampal epigenetic age compared to controls, with DNA methylation changes similar to those in humans with Down syndrome.

The paper uses single nucleus RNA-seq to analyze the hippocampus of a Down syndrome mouse model, identifying transcriptomic changes and a novel long-non-coding gene involved in cognitive phenotypes.

The paper examines changes in calcium-binding protein-expressing neurons in the anteroventral thalamic nuclei of individuals with Down syndrome compared to controls.

The paper shows that transcriptional dosage compensation is absent in Down syndrome using real and simulated data, and highlights issues with standard analysis methods.

This study investigates how Dyrk1A overexpression in mice affects neuronal network activity, finding that structural deficits, not over-inhibition, primarily impair network function.

This study examines the brain phenotype of Dp1Tyb mice, a Down syndrome model, revealing neuroanatomical and biochemical alterations compared to wild-type controls.

The paper identifies sex-specific DNA methylation differences in newborns with Down syndrome and major congenital heart defects compared to those without defects.

This study evaluates the effects of trisomy and GTE-EGCG treatment on multiple systems in a Down syndrome mouse model, finding that treatment exacerbates trisomic phenotypes rather than rescuing them.

This study investigates synaptic deficits in the prefrontal cortex of Ts65Dn mice, a model for Down syndrome, and compares them to mBACtgDyrk1a mice, revealing differences in synaptic plasticity and intrinsic neuronal properties.

This study integrates single-cell multi-omics data from human foetal blood to show that trisomy restructures enhancer-gene maps, leading to dysregulated erythroid differentiation and haematological abnormalities in Down's Syndrome.

The paper shows increased DYRK1A dosage causes mitochondrial dysfunction and congenital heart defects in Down syndrome, which can be mitigated by a DYRK1A inhibitor.