Certain genes may help protect at-risk people from Alzheimer’s disease

Monday, April 13, 2020 (Health Day News)-People with the gene called APOE4 are facing an increased risk of Alzheimer’s disease. But researchers have found that if you are lucky with another gene, the effects may be less.

Scientists have long known that the APOE gene is the strongest genetic effect on whether people will develop later years of Alzheimer’s disease. People with a genetic form called E4 have a higher than average risk.

However, not all APOE4 carriers will develop Alzheimer’s disease. It is important to understand what protects these people, says the study, co-author Dr. Michael Greicius, associate professor of neurology at Stanford University School of Medicine, California.

Based on his team’s findings, many may ride another gene called klotho. Among APOE4 carriers, those with “protected” Klotho are 30% less likely to develop Alzheimer’s disease by the age of 80.

Neurologist Dr. Dena Dubal stated that the klotho variant suggests that it may help the brain “fully avoid the harmful effects of APOE4.”

Dubal JAMA Neurology, Published the study online on April 13. She wrote an editorial accompanying the findings.

The klotho gene is named after the Greek fate and Zeus’ daughter, who was said to spin the thread of life. This is so-called because recent studies have shown that this gene is important in healthy aging, laboratory mice, and humans.

“It’s basically a gene for longevity,” Greicius said.

What’s not clear, he said, is how klotho counteracts some of the harm of APOE4. If researchers understood, Grisius added that it could lead to new treatments and methods to prevent Alzheimer’s disease.

We all inherit two copies of every gene. According to the US National Institute on Aging, about 25% of the population in the United States has one copy of APOE4, which has an Alzheimer’s risk three to four times higher than average. In a small percentage, two copies are made, which further increases the risk.

Grelot explained about klotho that it is best to inherit only one copy of the protection form. It seems to increase the level of Klotho protein in the blood. In addition, those who have one copy tend to live longer and be healthier than those who have or do not have two copies.

According to Greicius, the ideal Klotho scenario is as common as the APOE4 gene mutation. About a quarter of Americans have one copy of the protected form of the gene

In the current study, his team searched publicly available research databases and collected data for over 20,000 people over the age of 60.

APOE4 carriers who also had one copy of the protective Klotho variant had a 30% reduced chance of developing Alzheimer’s disease by the age of 80. However, there was no evidence that the Klotho variant protected people without the APOE4 variant.

“This suggests that there may be an interaction between the klotho variant and APOE4,” Greicius said.

It’s important to understand what’s going on, Duval said. At this point, she pointed out some clues from animal studies: In laboratory mice, higher Klotho levels enhance brain function.

“Maybe klotho, along with a healthy lifestyle, may be an effective treatment for APOE4 carriers to stop Alzheimer’s disease,” Duval speculated. “We need to take this path further.”

Glaciers agreed that raising the level of closo in the body could be beneficial. But he emphasized, no one knows if it really is.

The findings raise another question: Should APOE4 carriers be tested for their klotho genotype? Graceius said he first thought that more research was needed.

That was reflected in Rebecca Edelmeier, head of scientific engagement at the Alzheimer’s Association.

“I don’t think this can talk to your doctor today-there may be in the future,” Edelmeier said. She noted that researchers continue to delve into the genetics of Alzheimer’s disease, and said that other genes (and gene interactions) might prove to be key to the puzzle.

And there are lifestyle measures. Challenge your mind by eating healthy, exercising, managing health conditions such as high blood pressure and diabetes, and working mentally. According to Edelmeier, studies have shown that these generally help protect the aging brain.

For more information

The American Institute of Aging, Genetics of Alzheimer’s disease.