Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA140105 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Molecular Signatures Underlying Selective Regional Vulnerability to Alzheimer's Disease
| PRJNA329139 | ENA
Project description:To identify disease-related molecular processes that occur before the onset of detectable neuropathology in Alzheimer's disease (AD), we performed a comprehensive single-cell analysis of disease-related molecular sex differences in transcriptomic data from the neocortex of 24-week-old Tg2576 mice and wild-type littermate controls. Cell type-specific changes were investigated at the level of individual genes, pathways and gene regulatory networks. The analyses revealed significant cell-type-specific gene expression changes in individual genes, pathways and sub-networks, including sex-specific and sex-dimorphic changes in both upstream transcription factors and their downstream targets, before the onset of overt disease. The study opens a window into the molecular events that may determine sex-specific susceptibility to Alzheimer's disease and uncovers tractable target candidates for potential sex-specific precision medicine for AD.
2025-01-02 | GSE285694 | GEO
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)
2016-07-20 | E-GEOD-72782 | biostudies-arrayexpress
Project description:genes/pathways underlying lipoprotein homeostasis
| PRJNA87825 | ENA
Project description:Alzheimer's disease (AD) displays sex-specific differences in prevalence and progression, but the underlying molecular mechanisms remain unclear. To investigate sex-dependent molecular changes associated with tau pathology at a late disease stage, we performed single-cell RNA sequencing on cortical tissue from 17-month-old THY-Tau22 mice and wildtype littermates of both sexes. The analysis revealed extensive sex-specific and sex-dimorphic transcriptomic alterations across multiple cell types, with particularly pronounced changes in microglia and oligodendrocytes. Key pathways affected in a sex-dependent manner included RNA processing and splicing, stress response pathways, neurotransmitter signaling, and protein degradation pathways. Network analysis identified the genes Clu, Mbp, Fos and Junb as potential regulatory hubs. Multiple genes with established implications in AD, including the long non-coding RNA gene MALAT1, showed concordant sex-specific changes when compared with both earlier time points and human AD data. This study provides a comprehensive characterization of sex-dependent transcriptomic changes in late-stage tau pathology, revealing new insights into the interplay between AD-like pathology and biological sex.
2025-01-06 | GSE285506 | GEO