Scientists find how a rare FN1 mutation shields APOE ε4 carriers from Alzheimer's

Columbia University researchers uncovered a mechanism behind Alzheimer's resistance in people carrying the high-risk APOE ε4 variant. Excess fibronectin around brain blood vessels activates abnormal integrin and FAK signaling that disrupts the blood-brain barrier, and a rare FN1 mutation appears to limit this damage.

• Mice with APOE ε4 had nearly twice as much brain fibronectin as those with APOE ε3
• Raising fibronectin in astrocytes made the barrier leaky; lowering it improved barrier function
• The mechanism was confirmed in human tissue, 3D vessel cultures, zebrafish and mice
• The findings were published in Nature Aging