Newly Found Genetic Variant Defends Against Alzheimer’s Disease

Discovery could launch new types of drugs to prevent, treat the disease

April 9, 2024

Columbia researchers have discovered a genetic variant that reduces the odds of developing Alzheimer’s disease by up to 70% and may be protecting thousands of people in the United States from the disease. The discovery of the protective variant supports emerging evidence that the brain’s blood vessels play a large role in Alzheimer’s disease and could herald a new direction in therapeutic development.

“Alzheimer’s disease may get started with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear,” says Caghan Kizil, PhD, a co-leader of the study that identified the variant and associate professor of neurological sciences at Columbia University Vagelos College of Physicians and Surgeons.

The protective variant identified by the study occurs in a gene that makes fibronectin, a component of the blood-brain barrier, a lining surrounding the brain’s blood vessels that controls the movement of substances in and out of the brain. Fibronectin is usually present in the blood-brain barrier in very minute amounts, but it is increased in large amounts in people with Alzheimer’s disease. The variant identified in the fibronectin gene seems to protect against Alzheimer’s disease by preventing the buildup of excess fibronectin at the blood-brain barrier.

The researchers confirmed that hypothesis in a zebrafish model of Alzheimer’s disease and have additional studies in mice underway. They also found that reducing fibronectin in the animals increased amyloid clearance and improved other damage caused by Alzheimer’s disease.

These results give the idea that a therapy targeting fibronectin and mimicking the protective effect of the gene could lead to new types of drugs to prevent or treat Alzheimer’s disease.