WASHINGTON – For the first time, researchers have identified a genetic form of Alzheimer’s disease late in life – in people who inherit two copies of a worrying gene.
Scientists have long known that a gene called APOE4 is one of many things that can increase people’s risk for Alzheimer’s disease, 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 an underlying cause of the mind-stealing disease.
The findings mark a distinction with “profound implications,” said Dr. Juan Fortea, who led the study at the Sant Pau Research Institute in Barcelona, Spain.
Among them: Symptoms may begin seven to 10 years earlier than in other seniors who develop Alzheimer’s.
An estimated 15% of Alzheimer’s patients carry two copies of APOE4, meaning these cases “can be traced back to a cause and the cause is in the genes,” Fortea said. Until now, genetic forms of Alzheimer’s disease were thought to be just types that struck at much younger ages and accounted for less than 1% of all cases.
Scientists say the research makes it critical to develop treatments that target the APOE4 gene. Some doctors don’t offer the only drug shown to modestly slow the disease, Leqembi, to people with this pair of genes because they are especially prone to a dangerous side effect, said Dr. Reisa Sperling, co-author of the Harvard study. . -affiliated Brigham and Women’s Hospital in Boston.
Sperling looks for ways to prevent or at least delay Alzheimer’s and “this data to me says, wow, what an important group to be able to go after before they become symptomatic.”
But the news doesn’t mean people should rush to get a genetic test. “It’s important not to scare everyone who has a family history” of Alzheimer’s because this double gene is not behind most cases, she told the Associated Press.
More than 6 million Americans, and millions more around the world, have Alzheimer’s. Some genes are known to cause rare forms of “early onset,” mutations passed down through families that trigger symptoms at an unusually young age, around age 50. Some cases are also linked to Down syndrome.
But Alzheimer’s disease appears most often after age 65, especially in the late 70s and 80s, and it has long been known that the APOE gene – which also affects how the body handles fat – plays some role. There are three main varieties. Most people carry the APOE3 variant, which appears to neither increase nor decrease the risk of Alzheimer’s. Some carry APOE2, which provides some protection against Alzheimer’s disease.
APOE4 has long been labeled as the biggest genetic risk factor for late-life Alzheimer’s disease, with two copies more risky than one. It is estimated that around 2% of the global population has inherited one copy from each parent.
To better understand the gene’s role, Fortea’s team used data from 3,297 brains donated for research and from more than 10,000 people in Alzheimer’s studies in the US and Europe. They examined the symptoms and early features of Alzheimer’s disease, such as sticky amyloid in the brain.
People with two copies of APOE4 accumulated more amyloid by age 55 than those with just one copy or the “neutral” variety of the APOE3 gene, they reported in the journal Nature Medicine. At age 65, brain scans showed significant plaque buildup in nearly three-quarters of dual carriers — who were also more likely to have early Alzheimer’s symptoms around that age, rather than in their 70s or 80s.
Fortea said the underlying biology of the disease was remarkably similar to young inherited types.
It looks 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 all people with two APOE4 genes develop Alzheimer’s symptoms, and researchers need to know why, Sperling cautioned.
“It’s not really destiny,” she said.
The drug Leqembi works by eliminating some sticky amyloid, but Sperling said it’s not clear whether carriers of two APOE4 genes benefit because they have a very high risk of a side effect of the drug — dangerous brain swelling and bleeding. One research question is whether it would be better for them to start these medications earlier than other people.
Masliah said further research aims to develop gene therapy or drugs that specifically target APOE4. He said it is also crucial to understand the effects of APOE4 in diverse populations, as it has been studied primarily in white people of European descent.
As for genetic tests, for now they are typically only used to assess whether someone is a candidate for Leqembi or for people enrolling in Alzheimer’s disease research – especially studies of possible ways to prevent the disease. Sperling said the people most likely to carry two APOE4 genes had parents who contracted Alzheimer’s disease relatively early, in their 60s rather than their 80s.
___
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. AP is solely responsible for all content.
This story originally appeared on ABCNews.go.com read the full story
