A pericyte-to-myofibroblast transition links APOE4 to cerebrovascular degeneration.
APOE4 promotes cerebrovascular degeneration by inducing pericyte-to-myofibroblast transition, reducing pericyte coverage by 50% in human and mouse brains.
- Why it matters: Understanding how APOE4 contributes to cerebrovascular pathology is crucial because vascular degeneration is a key feature of Alzheimer's disease, yet its mechanisms remain unclear.
- What they did: Researchers created a single-cell transcriptomic atlas of human brain vasculature, identifying a shift from pericytes to myofibroblasts in APOE4 carriers and pinpointing TGF-β signaling as the driver.
- The result: Inhibiting TGF-β signaling restored pericyte coverage, decreased vascular fibrosis and amyloid accumulation, and offers a potential therapeutic target to mitigate cerebrovascular damage in AD.