In mice carrying APOE4, fibronectin around brain vessels was nearly double, and lowering it tightened the barrier

What the research found

Study (human tissue plus animals, not a treatment trial). Caghan Kizil and colleagues at Columbia University Irving Medical Center report in Nature Aging (2026; 6(9):1901; DOI 10.1038/s43587-026-01204-0). ScienceDaily carried it on 19 Oct 2026. Some people who carry APOE ε4, a common Alzheimer's risk variant present in about one in five people, stay mentally sharp into their 80s. Earlier work from the same group found a rare fibronectin (FN1) mutation in some of those carriers. This paper says APOE ε4 pushes fibronectin to build up around brain blood vessels. Mice engineered with human APOE ε4 had nearly twice as much fibronectin in the brain as mice with APOE ε3, and their blood-brain barrier was leakier. Raising human fibronectin in astrocytes was enough to make the barrier more permeable. Lowering it improved barrier function. The same pattern showed up in human Alzheimer's tissue, cerebrospinal fluid, stem-cell vessel models, zebrafish, and mice. Excess fibronectin was tied to abnormal integrin and focal adhesion kinase signals that scramble VEGF, HBEGF, and IGF1 communication. Fibronectin also has normal jobs in tissue repair, so blocking it everywhere is not a ready therapy. Not medical advice.

Evidence level: Animal study. Results in animals or cells often don't carry over to people.

Read the original at Columbia University / Nature Aging