New study finds that Alzheimer's disease may be caused in part by two copies of a single gene
Researchers have identified for the first time a genetic form of late-onset Alzheimer's disease in people who inherit two copies of a concerning gene.
Scientists have long known that a gene called APOE4 is one of many factors that can increase people's risk of Alzheimer's disease, including simply getting older. The majority of Alzheimer's disease cases occur after age 65. But a study published Monday suggests that for people who carry two copies of the Alzheimer's gene instead of one, it may not be a risk factor but the root cause of the heart-wrenching disease.
Dr Juan Fortea, who led the study at the Sant Pau Institute in Barcelona, Spain, said the findings showed a difference that had “deep implications”.
Among them is that symptoms may appear seven to 10 years earlier than other older people who develop Alzheimer's disease.
An estimated 15% of people with Alzheimer's disease have two copies of APOE4, meaning that these cases “can be traced back to the cause, and the cause is genetic,” Fortea said. Until now, hereditary Alzheimer's disease was thought to be the only type that occurs at a much younger age and accounts for less than 1% of all cases.
Scientists say this study makes it important to develop treatments that target the APOE4 gene. Some doctors believe that people with this gene pair are particularly prone to dangerous side effects, and that it has been shown to moderately slow the progression of the disease, said study co-author Leisa Sperling, Ph.D., from Harvard University. The only drug available, Requembi, is not available. Affiliated with Brigham and Women's Hospital in Boston.
Dr. Sperling is looking for ways to prevent or at least delay Alzheimer's disease, and “this data shows me how important it is to have a group that can be tracked before symptoms appear.”
But this news doesn't mean people should get genetic testing. “It's important not to scare everyone who has a family history” of Alzheimer's disease, she told The Associated Press. That's because this genetic combination is not behind most cases.
How does genetics affect Alzheimer's disease? More than 6 million Americans and millions more worldwide have Alzheimer's disease. A small number of genes are known to cause a rare “early-onset” form, where mutations are passed down in families and cause symptoms at an unusually young age, by age 50. Also, some cases are associated with Down syndrome.
However, Alzheimer's disease most often develops 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 processes fat) plays a role. It was getting worse. There are three main types. Most people carry the APOE3 variant, which does not appear to increase or decrease the risk of Alzheimer's disease. Some include her APOE2, which provides some protection against Alzheimer's disease.
APOE4 has long been considered the biggest genetic risk factor for late-life Alzheimer's disease, with two copies thought to be higher risk than one copy. It is estimated that about 2% of the world's population inherits a copy from each parent.
Study points to partial cause of Alzheimer's disease To better understand the role of this gene, Fortea's team looked at the brains of 3,297 people donated for study and participants in Alzheimer's disease studies in the U.S. and Europe. used data from more than 10,000 people. They looked at symptoms and early features of Alzheimer's disease, such as sticky amyloid in the brain.
People with two copies of APOE4 had accumulated more amyloid at age 55 than those with only one copy, or the “neutral” APOE3 gene variant, the study found. reported in the journal Nature Medicine. Brain scans by age 65 showed significant plaque buildup in nearly three-quarters of double carriers, and they also developed early symptoms of Alzheimer's disease around that age, rather than in their 70s or 80s. There was a high possibility that it would.
Fortea said the underlying biology of the disease is strikingly similar to the younger genotype.
Dr. Eliezer Masria of the National Institute on Aging said it was similar to “familial Alzheimer's disease.” “It's not just a risk factor.”
Importantly, Sperling cautioned, not everyone with two APOE4 genes will develop symptoms of Alzheimer's disease, and researchers need to know why.
“It's not fate at all,” she said.
How new findings could impact Alzheimer's disease research and treatment The drug Rekenbi works by removing sticky amyloid, but carriers of two APOE4 genes are less likely to receive the drug. Sperling said it's unclear whether it works because the risk of side effects (danger brain) is so high. swelling and bleeding. One research question is whether it is better to start taking such drugs earlier than others.
Masria said other research is aimed at developing gene therapies and drugs that specifically target APOE4. He said it is also important to understand the effects of APOE4 in diverse populations, as APOE4 has been primarily studied in Caucasian people of European descent.
When it comes to genetic testing, it's usually only done so far to assess whether someone is a candidate for Rekenbi or to evaluate people enrolled in Alzheimer's research, particularly research into ways to potentially prevent the disease. used. Sperling said people most likely to carry two APOE4 genes have parents who developed Alzheimer's disease relatively early in their lives, in their 60s rather than their 80s.