Rare FN1 Mutation May Shield the Brain From Alzheimer's Damage

Columbia researchers found that a rare fibronectin gene (FN1) variant protects APOE ε4 carriers from Alzheimer's by limiting fibronectin buildup around brain blood vessels. Excess fibronectin disrupts the blood-brain barrier, and the study in Nature Aging maps the mechanism and possible treatment targets.

• About one in five people carries at least one copy of APOE ε4
• Mice with human APOE ε4 had nearly twice the brain fibronectin of APOE ε3 mice
• Raising fibronectin in astrocytes alone made the barrier leaky
• Three paths proposed: block buildup, block integrin signals, or restore VEGF, HBEGF and IGF1