Project description:We used single-cell whole genome sequencing (scWGS) to assess aneuploidy in isolated neurons from the frontal cortex of control individuals. This experiment is related to E-MTAB-4184, which contains Alzheimer's disease samples.
Project description:We set up a 3D model based on iPSCs derived from patients with familial forms of Alzheimer’s disease (AD) and healthy non-demented control. We created cerebral organoids (COs), verified their ability to mimic AD in vitro, and used it to explore early events and the progression of AD pathogenesis. Our data reveal that despite similar expression of cell-type-specific genes during CO maturation in vitro, AD-iPSCs derived COs show limited tissue patterning and altered cellular development. These findings complement unique single-cell sequencing data of AD-iPSCs derived COs confirming this observation and uncovering that a sub-set of neurons in AD-iPSCs likely differentiates prematurely while at the same time retaining the expression of progenitor marker PAX6.
Project description:Single-cell RNA sequencing data from purified mouse microglia with and without 5xFAD Alzheimer's disease model and with and without Bace-1 knockout
Project description:This SuperSeries is composed of the following non-comparable subset Series which represent two different studies: GSE4226: Alzheimer's Disease peripheral blood mononuclear cell expression GSE4227: Alzheimer's disease and GSTM3 [Val255] single nucleotide polymorphism linkage with peripheral BMC expression Keywords: SuperSeries Refer to individual Series
Project description:Our study aimed to investigate the impact of germlineTrem2knockout in Tg-SwDI mice, a transgenic mouse model of cerebral amyloid angiopathy and Alzheimer's disease.
Project description:Forebrain microvasculature is defective in Alzheimer's disease. To model the role of cranial pericytes in influencing endothelial cell functions, we developed a method for cranial-pericyte derivation from iPSCs. Our studies reveal inherent defects in cranial pericytes from familial AD iPSC. We also demonstrate a similar pathophysiology in perimary pericytes isolated from sporadic AD patients that can be rescued.
2018-09-22 | GSE104141 | GEO
Project description:Single-cell Epigenome Analysis of the Alzheimer's Disease Brain
Project description:Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognitive function. Evidence suggests a role for epigenetic regulation, in particular the cytosine modifications 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC,) in AD. 5hmC is highly enriched in the nervous system and displays neurodevelopment and age-related changes. To determine the role of 5hmC in AD, we performed genome-wide analyses of 5hmC in DNA from prefrontal cortex of post-mortem AD as well as RNA-Seq to correlate changes in methylation status with transcriptional changes. We also utilized the existing AD fly model to further test the functional significance of these epigenetically altered loci. We identified 325 genes containing differentially hydroxymethylated loci (DhMLs) in both the discovery and replication datasets, and these are enriched for pathways involved in neuron projection development and neurogenesis. Of the 325 genes identified, 140 also showed changes in gene expression by RNA-Seq. Proteins encoded by genes identified in the current analysis form direct protein-protein interactions with AD-associated genes, expanding the network of genes implicated in AD. Furthermore, we identified AD-associated single nucleotide polymorphisms (SNPs) located within or near DhMLs, suggesting that these SNPs may identify regions of epigenetic gene regulation that play a role in AD pathogenesis. Finally using the existing AD fly model we showed that some of these genes could modulate the toxicity associated with AD. Our data implicate neuron projection development and neurogenesis pathways as potential targets in AD. These results indicate that incorporating epigenomic and transcriptomic data with GWAS data can expand the known network of genes involved in disease pathogenesis. Combination of epigenome profiling and Drosophila model enables us to identify the epigenetic modifiers of Alzheimer's disease. University of Kentucky Alzheimer's Disease Research Center (3 control, 3 Alzheimer's) and Emory University Alzheimer's Disease Research Center (2 control, 2 Alzheimer's)
