by WASHINGTON (AP) – For the first time, researchers have identified a genetic form of late-life Alzheimer’s disease – in people who inherit two copies of an anxiety gene.
Scientists have long known that a gene called APOE4 is one of many things that can increase people’s risk for Alzheimer’s, including simply getting older. The vast majority of Alzheimer’s cases occur after age 65. But research published Monday suggests that for people who carry not one but two copies of the gene, it’s more than a risk factor, it’s a root cause of the mental illness. -robbing it.
The findings show a distinction that has “profound implications,” said Dr. Juan Fortea, who led the study at the Sant Pau Research Institute in Barcelona, Spain.
Among them: Symptoms can start seven to 10 years earlier than in other older adults who develop Alzheimer’s.
An estimated 15% of Alzheimer’s patients carry two copies of APOE4, meaning that those cases “can be traced back to a cause and the cause is in the genes,” Fortea said. Until now, the genetic forms of Alzheimer’s were thought to be only types that strike at much younger ages and make up less than 1% of all cases.
Scientists say the research is critical to developing treatments that target the APOE4 gene. Some doctors will not offer the only drug that has been shown to slow the disease to a moderate extent, Leqembi, to people with the gene pair because they are more likely to have a dangerous side effect, said Dr. Reisa Sperling, study co-author at Harvard-affiliated Brigham and Women’s Hospital in Boston.
Speirling looks for ways to prevent or at least slow down Alzheimer’s and “this data says to me, it’s important to be able to go after it before it becomes a symptom”.
But the news doesn’t mean people should race for gene testing. “It is important not to scare everyone who has a family history” of Alzheimer’s because this gene duo is not behind most of the cases, she told the Associated Press.
HOW DO GENETICS INFLUENCE ALZHEIMER?
More than 6 million Americans, and millions more worldwide, have Alzheimer’s. A handful of genes are known to cause rare “early onset” forms, mutations that run through families that trigger the unusual symptoms young, under the age of 50. Some cases are also associated with Down syndrome.
But Alzheimer’s often strikes after 65, especially in the late 70s to the 80s, and the APOE gene – which also affects how the body handles fats – has long been known to play a role. There are three main types. Most people carry the APOE3 variant which appears to neither increase nor decrease Alzheimer’s risk. Some carry APOE2, which provides some protection against Alzheimer’s.
APOE4 has long been labeled the greatest genetic risk factor for late-life Alzheimer’s, with two copies leading to greater risk than one. It is estimated that about 2% of the world’s population inherited a copy from each parent.
RESEARCH POINTS TO THE CAUSE OF UNDERGIVING OF ALZHEIMER’S
To better understand the role of the gene, Fortea’s team used data from 3,297 brains donated for research and from more than 10,000 people in US and European Alzheimer’s studies. They examined early signs and hallmarks of Alzheimer’s such as sticky amyloid in the brain.
People with two copies of APOE4 were accumulating more amyloid at age 55 than those with only one copy or the “neutral” form of the APOE3 gene, they reported in the journal Nature Medicine. By the age of 65, brain scans showed a significant increase in plaque in nearly three-quarters of those double carriers – who were also more likely to have the onset of Alzheimer’s symptoms around that age rather than in their 70s or 80s.
Fortea said the basic biology of the disease was very similar to young hereditary strains.
It seems more like a “familial form of Alzheimer’s,” said Dr. Eliezer Masliah of the National Institute on Aging. “It’s not just a risk factor.”
Importantly, not everyone with two APOE4 genes develops Alzheimer’s symptoms and researchers need to find out why, Sperling cautioned.
“It’s not absolute destiny,” she said.
HOW THE NEW FINDINGS COULD AFFECT ALZHEIMER’S RESEARCH AND TREATMENT
The drug Leqembi works by clearing some sticky amyloid, but Sperling said it’s unclear if carriers of two APOE4 genes benefit because they have such a high risk of the drug’s side effect — dangerous brain swelling and bleeding. One research question is whether they would be better off starting such drugs earlier than others.
Masliah said other research aims to develop gene therapy or drugs to specifically target APOE4. He said it is also important to understand the effects of APOE4 in different populations since it has been studied primarily in white people of European ancestry.
As for gene tests, they are currently only typically used to assess whether someone is a candidate for Leqembi or by people enrolling in Alzheimer’s research – particularly studies of possible ways to prevent the disease. Sperling said that the people most likely to carry two APOE4 genes had parents who got Alzheimer’s relatively early, in their 60s rather than their 80s.
___
The Associated Press Health and Science Section is supported by the Howard Hughes Medical Institute Science and Media Education Group. The AP is solely responsible for all matters.
