New research has found that nearly all people with two copies of the gene variant APOE4 develop biological markers of Alzheimer's disease, suggesting the gene may be its own, distinct form of the disease rather than only a risk factor.
Under previous understandings about genetic forms of the disease, about 1 in 50 Alzheimer's cases were thought to be caused by genetics. Under researchers' latest findings, 1 in 6 cases would be considered inherited, experts told CNN.
The study, published May 6 in Nature Medicine, was based on samples from more than 3,200 brain donors from the National Alzheimer's Coordinating Center, as well as more than 10,000 individuals who participated in clinical trials in Europe and the U.S. Of the people who had two copies of the APOE4 gene, 95% had biological markers of Alzheimer's disease by the time they were 65, the study found. Many patients also started to experience symptoms of cognitive decline at age 65, earlier than most people without the APOE4 gene variant.
"These data represent a reconceptualization of the disease or what it means to be homozygous for the APOE4 gene," Juan Fortea, MD, PhD, lead study author and director of the memory unit at Sant Pau Research Institute in Barcelona, Spain, said in a May 6 news release. "This gene has been known for over 30 years and it was known to be associated with a higher risk of developing Alzhiemer's disease, but now we know that virtually all individuals with this duplicated gene develop Alzheimer's biology."
The reclassification proposed by researchers could have significant implications for drug development and clinical trials, given that many people with two copies of the gene face higher safety risks from drugs that target amyloid, experts told The New York Times.
About 2% of the population carries both copies of the gene, which, per the new classification, would make it one of the most common inherited diseases globally.