The Brain's Blood Vessels May Hold a Key to Alzheimer's—and Protection From It

A new study is shedding light on how changes in the brain’s blood vessels may contribute to Alzheimer’s disease—and how naturally occurring genetic protection could point toward new therapeutic strategies. Led by Caghan Kizil, PhD, MSc, the study identifies a mechanism by which excess fibronectin can disrupt the blood-brain barrier and promote changes associated with Alzheimer’s disease.

The work builds on an earlier research by Dr. Kizil and Badri N. Vardarajan, PhD, who found that a rare mutation in the FN1 gene, which encodes fibronectin, appeared to protect some people carrying the high-risk APOE ε4 gene from developing Alzheimer’s disease. Prabesh Bhattarai, PhD, was first author on the earlier work and co-first author with Elanur Yilmaz on the most recent study.

“This new study takes us from a genetic clue to a disease mechanism,” says Kizil, professor of neurological sciences in the Department of Neurology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Vagelos College of Physicians and Surgeons. “We knew that changes in fibronectin could protect against Alzheimer's, but we didn't know why excess fibronectin was harmful in the first place. This study gives us that detailed mechanism—and with it, ideas for how to reproduce that natural protection.”

Read more about the study and its implications in the CUIMC Newsroom.