APOE4 drives cerebrovascular degeneration by converting pericytes into scar-forming myofibroblasts
APOE4, the strongest genetic risk factor for late-onset Alzheimer’s disease, turns the cells that normally support brain blood vessels into scar-forming cells. Those cells lay down fibronectin, which stiffens the vessels and traps amyloid around them. Blocking a signaling pathway called TGF-β reversed this process in human brain models and aged APOE4 mice, restoring vessel support and reducing both scarring and vascular amyloid. The findings suggest TGF-β signaling and fibronectin buildup as possible targets for protecting blood flow in the brain of people at high genetic risk.
