Mutant genes prevent people at risk from developing Alzheimer’s disease

Wednesday, June 1, 2022 (HealthDay News)-The APOE4 gene is the most potent gene factor that increases the risk of late onset. Alzheimer’s disease..

“One APOE4 copy increases the risk by 2-3 times, and two APOE4 copies increases the risk by about 10 times,” said Dr. Michael Gracieus, professor of neurology at Stanford University School of Medicine. increase.

But the story gets a little more complicated-in a way that can potentially save millions of inherited brains. APOE4 gene..

The international research team led by Graceius is actually Alzheimer’s disease Risks posed by the APOE4 gene.

Change only one R251G variant amino acid Although it is an apolipoprotein E (APOE) gene, its simple changes appear to neutralize the risk of Alzheimer’s disease, which is usually caused by APOE4, the researchers said.

Unlike most people with APOE4, people with the R251G mutation are not at increased risk of developing Alzheimer’s disease, according to a Stanford University news release.

“Perhaps one in 1,000 people who carry that high-risk gene has the same copy of the gene for the protective variant that essentially takes the high risk and cuts it,” Greicius said.

This finding could help unravel the 30-year-old mystery of why APOE4 is a very strong risk factor for Alzheimer’s disease, Greicius said.

First study linking APOE4 to degenerative diseases Brain disease Published in the 1990s, no one yet understands how genes actually increase risk.

“It doesn’t take long for basic scientists to insert this exact same gene variant into a cell model and ask how APOE behaves differently from this variant,” Greicius said in the lab. The researchers added that the R251G mutant could also be inserted into mice.

“The mouse model takes years to breed and age, but it should all be done sooner now,” Graceius said. “So I’m really excited to spread the word and I’m trying to make some of my basic science colleagues in this field really jump into the mechanics.”

“The exact role of APOE in Alzheimer’s disease is not well understood,” said Heather Snyder, vice president of medicine and science at the Alzheimer’s Association.

“The idea that there are additional variants of APOE that may reduce the risk of Alzheimer’s disease is very interesting,” Snyder said. “A better understanding of this biology is crucial to gaining insights from these new mutants that may lead to treatable targets.”

Published in the May 31st issue of the journal for this study JAMA Neurology, Gracieus and his colleagues have mined a vast amount of genetic data, including more than 544,000. These included genetic analysis of more than 67,000 people with Alzheimer’s disease, 28,000 with close relatives of Alzheimer’s disease, and 340,000 healthy people to compare with them.

Everyone has a version of the APOE gene, which primarily helps control the use of cholesterol around the body, Greicius said. cholesterol As an important component of the cell wall, it is important for normal cell function.

According to Graceius, the protein produced by APOE4 has two main parts, one that binds to the protein and the other that binds to cholesterol.

“This new protective variant described here is actually part of a protein that binds to lipids such as cholesterol and other fats,” Greicius said. “It is in a separate region of the protein APOE4.”

The research team also investigated a second protective mutation that reduced the risk of Alzheimer’s disease by about 60%, the study reports. The mutant, called V236E, is co-inherited with the common APOE3 gene and provides the same level of protection as APOE2.

“If we can better understand how mutations reduce risk, this may open the door to biology that is the target of possible therapeutic and / or therapeutic development,” Snyder said. Stated.

For more information

The National Institutes of Health details the genetic risk of Alzheimer’s disease.