A rare mutation may keep a major Alzheimer’s risk gene from damaging the brain’s protective barrier.

About one in five people carries at least one copy of APOE ε4, the strongest common genetic risk factor for Alzheimer’s disease. Yet some carriers remain mentally sharp into their 80s. Columbia researchers previously identified a rare variant in the fibronectin gene (FN1) that may help explain their resilience.

Fibronectin helps support the structure of tissues, but too much of it can collect around the brain’s blood vessels in people with APOE ε4. The protective variant appears to limit that buildup. A new study in Nature Aging investigates why that matters and whether the process could offer a target for treatment.