GSE264648 Characterization of premature cell senescence in Alzheimer ’s disease using single nuclear transcriptomics

Contributors : Nurun Fancy ; Amy M Smith ; Alessia Caramello ; Stergios Tsartsalis ; Karen Davey ; Robert C Muirhead ; Aisling McGarry ; Marion Jenkins ; Eleonore Schneegans ; Vicky Chau ; Michael Thomas ; Sam Boulger ; To K Cheung ; Emily Adair ; Marianna Papageorgopoulou ; Nanet Willumsen ; Combiz Khozoie ; Diego Gomez-Nicola ; Johanna Jackson ; Paul M MatthewsSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAging is associated with cell senescence and is the major risk factor for AD. We characterized premature cell senescence in post mortem brains from non-diseased controls (NDC) and donors with Alzheimer ’s disease (AD) using imaging mass cytometry (IMC) and single nuclear RNA (snRNA) sequencing (>200,000 nuclei). We found increases in numbers of glia immunostaining for galactosidase beta (>4-fold) and p16INK4A (up to 2-fold) with AD relative to NDC. Increased glial expression of genes related to senescence was associated with greater -amyloid load. Prematurely senescent microglia downregulated phagocytic pathways suggesting reduced capacity for -amyloid clearance. Gene set enrichment and pseudo-time trajectories described extensive DNA double-strand breaks (DSBs), mitochondrial dysfunction and ER stress associated with inc reased β-amyloid leading to premature senescence in microglia. We replicated these observations with independent AD snRNA-seq datasets. Our results describe a burden of senescent glia with ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research