Replicative senescence dictates the emergence of disease-associated microglia and contributes to Aβ pathology.

ABSTRACT: The sustained proliferation of microglia is a key hallmark of Alzheimer's disease (AD), accelerating its progression. Here, we aim to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesizing that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We show that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterized by increased βgal activity, a senescence-associated transcriptional signature, and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. The prevention of early microglial proliferation hinders the development o

SUBMITTER: Hu Y 

PROVIDER: S-EPMC8206957 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature