A gene variant may protect those with genetic predisposition for Alzheimer's disease

There’s a gene variant that can protect individuals who are genetically at higher risk for Alzheimer’s disease, according to a new study published on April 13th in JAMA Neurology.

Researchers found that for the 15 percent of individuals at high risk of developing Alzheimer's because of carrying the harmful variant of the ApoE4 gene a variation in a completely different gene may help protect them.

Michael Greiciusis, MD MPH, is the senior author of the study and an associate professor of neurology and director of the Stanford Center for Memory Disorders. The first author of the study is Michael Belloy, PhD, a postdoctoral scholar.

"While 15% of healthy people have the ApoE4 gene variant, it's present in more than 50% of Alzheimer's patients," said Greicius. "One copy of ApoE4 triples or quadruples your risk, compared with no copies. If you're carrying two copies, your risk goes up tenfold."

Just having ApoE4 doesn’t mean you will get Alzheimer’s Disease. What Greicius and his team showed is having another variation in a completely different gene protects ApoE4 carriers from Alzheimer’s. This new finding could help accurately predict who is at the greatest risk for the disease.

Greicius found that individuals with the ApoE4 risk factor surviving into their 80’s and 90’s carry a genetic variant of a protein called Klotho. Klotho when present in high levels in animal studies, predicts longevity. Having one copy of a genetic variant results in high amounts of the Klotho protein which affords protection from Alzheimer’s Disease.

"In this ApoE4 carrier group, carrying one copy -- but not two -- of the Klotho variant reduced Alzheimer's risk by 30%," said author Michael Belloy.

This could be an important finding for drug companies as they design clinical trials. Researchers say they may want to exclude patients with a single Klotho copy to maximize the contrast in outcomes for ApoE4 positive participants involved with experimental treatments.