Alzheimer's risk gene APOE4 damages brain vessels, but damage may be reversible

Mount Sinai researchers found that APOE4, the strongest genetic risk factor for Alzheimer's, turns pericytes into scar-producing cells, causing vascular fibrosis and amyloid buildup around brain vessels. Blocking TGF-β signaling reversed the damage in aged APOE4 mice, suggesting the process is therapeutically reversible.

• APOE4 converts pericytes into scar-producing cells, driving vascular fibrosis
• Blocking TGF-β restored pericyte coverage and cut amyloid in aged mice
• APOE4 raises cholesterol in astrocytes, impairing clearance of alpha-synuclein
• Work relied on miBrains, 3D human brain tissue grown from stem cells