Scientists are proposing a new way of understanding the genetics of Alzheimer’s disease, which would allow us to consider that up to a fifth of patients are affected by a form of the disease of genetic origin.
Currently, the vast majority of cases of Alzheimer’s do not have a clearly identified cause. The new designation, proposed in a study released Monday, could expand the scope of efforts to develop treatments, including gene therapy, and affect the design of clinical trials.
It could also mean that hundreds of thousands of people in the United States alone could, if they wanted, be diagnosed with Alzheimer’s disease before developing symptoms of cognitive decline, although there is currently no no treatment for people at this stage.
The new classification would make this type of Alzheimer’s disease one of the most common genetic diseases in the world, according to medical experts.
“This reconceptualization that we are proposing does not affect a small minority of people,” said Dr. Juan Fortea, study author and director of the Sant Pau Memory Unit in Barcelona, Spain. “Sometimes we say we don’t know the cause of Alzheimer’s disease,” but, he says, that would mean that about 15 to 20 percent of cases “can be attributed to a cause, and the cause is in the genes. »
The idea involves a genetic variant called APOE4. Scientists have long known that inheriting one copy of the variant increases the risk of developing Alzheimer’s disease, and that people with two copies, inherited from each parent, have a significantly increased risk.
THE new study, published in the journal Nature Medicine, analyzed data from more than 500 people with two copies of APOE4, a significantly larger pool than in previous studies. The researchers found that almost all of these patients developed the biological pathology of Alzheimer’s disease, and the authors say that two copies of APOE4 should now be considered a cause of Alzheimer’s disease, not just one risk factor.
Patients also developed Alzheimer’s disease relatively young, according to the study. By age 55, more than 95 percent had biological markers associated with the disease. By age 65, almost all had abnormal levels of a protein called amyloid that forms plaques in the brain, a hallmark of Alzheimer’s disease. And many began developing symptoms of cognitive decline at age 65, younger than most people without an APOE4 variant.
“The crucial point is that these people often show symptoms 10 years earlier than other forms of Alzheimer’s disease,” said Dr. Reisa Sperling, a neurologist at Mass General Brigham in Boston and an author of the study.
She added: “By the time they are recovered and diagnosed clinically, because they are often younger, they have more pathologies. »
People with two copies, known as APOE4 homozygotes, make up 2 to 3 percent of the general population, but make up about 15 to 20 percent of people with Alzheimer’s dementia, experts say. People who own a copy represent about 15 to 25 percent of the general population…
