Fig. 1

Proposed mechanism of the TREM2-APOE axis-mediated microglial senescence among previously reported microglial phenotypes. Accumulated DNA damage can dysregulate RNA metabolism and proteostasis, leading to accumulation of cytoplasmic aggregates and disruption of nucleocytoplasmic transport. Furthermore, chronic exposure to extracellular protein aggregates induces autophagy, mitochondrial dysfunction, and secretion of SASPs, with a primary focus on the TREM2-APOE axis. Created with Biorender.com