The genetic variant reduces the likelihood of Alzheimer’s disease by 70%.

Besides age and lifestyle, genetics can play a big role when it comes to the development of dementia such as Alzheimer’s disease.

It is known that a number of genetic mutations can make a person more susceptible. Researchers at Columbia University have found that others may do just the opposite. According to their recent findings, the presence of certain gene reduces the likelihood of developing Alzheimer’s disease by up to 70%.

“Alzheimer’s disease may start with amyloid deposits in the brain, but disease manifestations are the result of changes that occur after the deposits appear,” Dr. Kagan Kizil, co-principal investigator of the study that identified the variant, said in a press release.

“Our findings suggest that some of these changes occur in the brain’s vasculature and we may be able to develop new therapies that mimic the protective effect of the gene to prevent or treat the disease,” says Associate Professor of Neurological Sciences at the University. Vagelos College of Physicians and Surgeons, Columbia University.

Up to 3% of the US population may be carriers of the protective gene

A total of 75 genes are associated with an increased risk of the disease. So people with 2 copies of the APOEe4 gene They are 8 to 12 times more likely to develop this type of dementia, according to the Mayo Clinic.

But there are also cognitively healthy older people with APOE4. The research team’s hypothesis was that APOEe4 carriers without dementia They may carry genetic variations that may protect them from developing cognitive impairment.

To test this, the scientists sequenced the genomes of several hundred APOEe4 carriers over 70 years of age from different ethnic groups, including people with and without Alzheimer’s disease. They used whole genome sequencing (WGS) data from patients participating in the Washington Heights/Inwood Columbia Aging Project, an ongoing study conducted by the Columbia University Department of Neurology for more than 30 years.

Protective variant identified occurs in the gene that makes fibronectincomponent of the blood-brain barrier, a membrane that surrounds the brain’s blood vessels and controls the movement of substances into and out of the brain.

After discovering it, the Columbia team published their results in a journal. preprint so that other researchers can consult them. Another group from Stanford and Washington universities repeated the study in an independent cohort of APOEe4 carriers, mostly of European descent.

“They found the same fibronectin variant, which confirmed our findings and gave us even more confidence in our result,” says study co-leader Dr. Badri N. Vardarajan.

According to researchers, from 1% to 3% Among APOEe4 carriers in the United States—approximately 200,000 to 620,000 people—may also be carriers of the protective mutation.

A new approach to treatment?

As explained in the press release, fibronectin is usually present in very small amounts but increases significantly in people with Alzheimer’s disease. A variant identified in the fibronectin gene appears to protect against the disease. preventing the accumulation of excess fibronectin in the blood-brain barrier.

“This led us to think that excess fibronectin may interfere with the removal of amyloid deposits from the brain,” says Kizil.

The researchers confirmed this hypothesis in a zebrafish model of the disease and are conducting additional studies in mice. So far, they have found that reducing fibronectin in animals increases amyloid clearance and reduces other damage caused by this dementia.

Newer treatments for Alzheimer’s disease directly target amyloid deposits and are very effective at removing them through the immune system. However, simply removing deposits in this manner will not improve symptoms or reverse other damage.

“Maybe we’ll have to start removing amyloid much earlier and we believe this can be done through the bloodstream,” adds Dr. Richard Mayeux, professor of neurology. “That’s why we’re very excited about the discovery of this variant of fibronectin, which could be a good target for drug development.”