For the first time, researchers have identified a genetic form of late-in-life Alzheimerās disease ā in people who inherit two copies of a worrisome gene.
Scientists have long known a is one of many things that can increase peopleās risk for Alzheimer's, including simply getting older. The vast majority of Alzheimerās 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-robbing disease.
The findings mark a distinction with āprofound implications,ā said Dr. Juan Fortea, who led the study at the Sant Pau Research Institute in Barcelona, Spain.
Among them: Symptoms can begin seven to 10 years sooner than in other older adults who develop Alzheimerās.
An estimated 15% of Alzheimerās patients carry two copies of APOE4, meaning those cases ācan be tracked back to a cause and the cause is in the genes,ā Fortea said. Until now, genetic forms of Alzheimerās were thought to be only types that strike at much younger ages and account for less than 1% of all cases.
Scientists say the research makes it critical to develop treatments that target the APOE4 gene. Some doctors wonāt offer the only drug that has been shown to modestly slow the disease, Leqembi, to people with the gene pair because theyāre especially prone to a dangerous side effect, said Dr. Reisa Sperling, a study co-author at Harvard-affiliated Brigham and Womenās Hospital in Boston.
Sperling hunts ways to prevent or at least delay Alzheimerās and āthis data for me says wow, what an important group to be able to go after before they become symptomatic.ā
But the news doesnāt mean people should race for a gene test. āItās important not to scare everyone who has a family historyā of Alzheimerās because this gene duo isnāt behind most cases, she told The Associated Press.
How do genetics affect Alzheimer's?
More than 6 million Americans, and millions more worldwide, have Alzheimerās. A handful of genes are known to cause rare āearly-onsetā forms, mutations passed through families that trigger symptoms unusually young, by age 50. Some cases also are linked to Down syndrome.
But Alzheimerās most commonly strikes after 65, especially in the late 70s to 80s, and the APOE gene ā which also affects how the body handles fats -- was long known to play some role. There are three main varieties. Most people carry the APOE3 variant that appears to neither increase nor decrease Alzheimerās risk. Some carry APOE2, which provides some protection against Alzheimerās.
APOE4 has long been labelled the biggest genetic risk factor for late-in-life Alzheimerās, with two copies risker than one. About 2% of the global population is estimated to have inherited a copy from each parent.
Research points to a cause for a subset of Alzheimer's
To better understand the geneās role, Forteaās team used data from 3,297 brains donated for research and from over 10,000 people in U.S. and European Alzheimerās studies. They examined symptoms and early hallmarks of Alzheimerās such as sticky amyloid in the brain.
People with two APOE4 copies were accumulating more amyloid at age 55 than those with just one copy or the āneutralā APOE3 gene variety, they reported in the journal Nature Medicine. By age 65, brain scans showed significant plaque buildup in nearly three-quarters of those double carriers ā who also were more likely to have initial Alzheimerās symptoms around that age rather than in the 70s or 80s.
Fortea said the disease's underlying biology was remarkably similar to young inherited types.
It appears more like āa familial form of Alzheimerās,ā said Dr. Eliezer Masliah of the National Institute on Aging. āIt is not just a risk factor.ā
Importantly, not everyone with two APOE4 genes develops Alzheimerās symptoms and researchers need to learn why, Sperling cautioned.
āItās not quite destiny,ā she said.
How the new findings may affect Alzheimer's research and treatment
The drug Leqembi works by clearing away some sticky amyloid but Sperling said itās not clear if carriers of two APOE4 genes benefit because they have such a high risk of a side effect from the drug ā dangerous brain swelling and bleeding. One research question is whether theyād do better starting such drugs sooner than other people.
Masliah said other research aims to develop gene therapy or drugs to specifically target APOE4. He said it's also crucial to understand APOE4ās effects in diverse populations since itās been studied mostly in white people of European ancestry.
As for gene tests, for now theyāre typically used only to evaluate if someoneās a candidate for Leqembi or for people enrolling in Alzheimerās research ā especially studies of possible ways to prevent the disease. Sperling said the people most likely to carry two APOE4 genes had parents who both got Alzheimerās relatively early, in their 60s rather than 80s.
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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Instituteās Science and Educational Media Group. The AP is solely responsible for all content.
