Aging-Related Decline of Astrocytic APOE Expression via Extracellular Vesicle

APOE, a well-established genetic risk factor for Alzheimer's disease, is also closely associated with the aging process. Previous studies have demonstrated age-related declines in APOE expression within astrocytes. To investigate the mechanisms underlying this reduction, in this study, we performed small RNA sequencing on extracellular vesicles (EVs) derived from human fetal brain astrocytes. Our findings reveal miR-let-7b, enriched in astrocyte-derived EVs, as a key mediator of age-related APOE downregulation. Furthermore, we uncover a novel role for APOE in regulating astrocyte senescence, providing new insights into the molecular interplay between aging and neurodegenerative disorders. Overall design: small RNA profiling of EVs released from human fetal brain-derived astrocytes