APOE4 promotes cerebrovascular fibrosis and amyloid deposition via a pericyte-to-myofibroblast transition.

ABSTRACT: Cerebrovascular disease is a major but poorly understood feature of Alzheimer's disease (AD). The strongest genetic AD risk factor, APOE4, is associated with cerebrovascular degeneration, including vascular amyloid deposition and fibrosis. To uncover how APOE4 promotes cerebrovascular pathology, we generated a single-cell transcriptomic atlas of human brain vasculature. In APOE4 carriers, pericyte abundance was significantly reduced and accompanied by the emergence of a myofibroblast-like cell population co-expressing contraction and extracellular matrix genes. Immunostaining confirmed non-vascular myofibroblasts in APOE4 human and mouse brains. We show that APOE4 pericytes transition into myofibroblasts that secrete fibronectin, which promotes vascular amyloid accumulation. Computational

SUBMITTER: Schuldt BR 

PROVIDER: S-EPMC12439990 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature