Somatic cancer driver mutations are enriched and associated with inflammatory states in Alzheimer's disease microglia.

ABSTRACT: Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by progressive neuronal loss and pathological accumulation of the misfolded proteins amyloid-β and tau^1,2. Neuroinflammation mediated by microglia and brain-resident macrophages plays a crucial role in AD pathogenesis^1-5, though the mechanisms by which age, genes, and other risk factors interact remain largely unknown. Somatic mutations accumulate with age and lead to clonal expansion of many cell types, contributing to cancer and many non-cancer diseases^6,7. Here we studied somatic mutation in normal aged and AD brains by three orthogonal methods and in three independent AD cohorts. Analysis of bulk RNA sequencing data from 866 samples from different brain regions reveal

SUBMITTER: Huang AY 

PROVIDER: S-EPMC10802273 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature