Microglial States Are Susceptible to Senescence and Cholesterol Dysregulation in Alzheimer's Disease.

ABSTRACT: Cellular senescence is a major contributor to aging-related degenerative diseases, including Alzheimer's disease (AD), but much less is known about the key cell types and pathways driving senescence mechanisms in the brain. We hypothesized that dysregulated cholesterol metabolism is central to cellular senescence in AD. We analyzed single-cell RNA-seq data from the ROSMAP and SEA-AD cohorts to uncover cell type-specific senescence pathologies. In ROSMAP snRNA-seq data (982,384 nuclei from postmortem prefrontal cortex), microglia emerged as central contributors to AD-associated senescence phenotypes among non-neuronal cells. Homeostatic, inflammatory, phagocytic, lipid-processing, and neuronal-surveillance microglial states were associated with AD-related senescence in both ROSMAP (152,459

SUBMITTER: Li B 

PROVIDER: S-EPMC12507412 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature