Genetic variant reduces chance of Alzheimer’s disease

A new genetic variant will reduce the likelihood of developing Alzheimer’s disease by almost by 70%this was discovered by researchers from Columbia University, who emphasize that this variant may protect against disease.

Specifically, this option would allow “toxic forms of amyloid to leave the brain and cross the blood-brain barrier,” supporting growing evidence that “Blood vessels in the brain play an important role in Alzheimer’s disease and may mark a new direction in the development of therapy,” the university explains in a note.

In this sense, Kagan Kizil, assistant professor of neurological sciences at Columbia University’s Vagelos College of Physicians and Surgeons and co-principal investigator of the study that identified this variant, published in the journal Acta Neuropathologyexplains that these results “suggest that some of these changes occur in the brain vasculature and that we can develop new therapies that mimic the protective effect of the gene to prevent or treat disease.“.

According to the study, this protective variant is produced by “a gene that produces fibronectin

a component 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,” they explain.

In people with Alzheimer’s disease fibronectin increases in large quantities in the blood-brain barrier, which “led us to think that excess fibronectin may be interfering with the removal of amyloid deposits from the brain,” Kizil said. It was also found that “reducing fibronectin in animals increases amyloid clearance and reduces other damage caused by Alzheimer’s disease.”

With this in mind, Richard Maillet, professor of neurology and Gertrude H. Sergievsky Professor and co-author of the study, explained that “these results gave us the idea that therapies targeting fibronectin and mimicking the protective variant could provide strong protection against diseases“.

In this sense, they emphasize that although the most innovative treatments for Alzheimer’s disease directly target amyloid deposits and are effective in eliminating them through the immune system, “they just Removing deposits in this manner does not improve symptoms or reverse other damage.

“.

That is why they are considering the option “start removing amyloid much earlier and we think this can be done through the bloodstream,” explained Maillet, who was “excited about the discovery of this variant of fibronectin, which could be a good target for drug development.”

Protective gene in people resistant to Alzheimer’s disease

The researchers also highlight another discovery they made, namely that They found a protective variant in people who never developed symptoms of Alzheimer’s disease.but they inherited form e4 of the APOE gene, which increases the risk of this. These individuals “can tell us a lot about the disease and what genetic and nongenetic factors may provide protection,” said Badri N. Vardarajan, assistant professor of neurological sciences and co-author of the study.

So they calculated that This mutation reduces the likelihood of developing Alzheimer’s disease by 71%. in APOE4 carriers and prevent the disease in about 4 years in those people who will develop it, they note. And although this variant was found in APOEe4 carriers, they say it may protect against Alzheimer’s disease in people with other forms of APOE.

“Everything, that reduce excess fibronectin “should provide some protection, and a drug that provides this could be an important step forward in the fight against this debilitating disease,” they conclude.