Cholesterol buildup in APOE4 astrocytes seeds neuronal α-synuclein pathology in miBRAIN tissue
APOE4, the gene that most strongly raises the risk of late-onset Alzheimer’s disease, can cause cholesterol to build up in astrocytes, the support cells that help clear waste from the brain. That extra cholesterol clogs their disposal system, so a protein called alpha-synuclein is not broken down properly and instead spreads into nerve cells, where it forms harmful deposits also seen in Lewy body dementia and Parkinson’s disease. In lab-grown human brain tissue, lowering that cholesterol buildup restored waste clearance and reduced the protein deposits in nerve cells. The results suggest cholesterol handling in astrocytes as a possible target for people at high genetic risk, though this approach has not yet been tested in patients.
