Scientists studying families with early-onset Alzheimer's disease have discovered that some have a genetic quirk that delays early symptoms by up to five years.
The discovery offers a new way to fight the mind-robbing disease. If researchers can reveal how a single copy of a very rare genetic variant provides at least some protection.
“This opens up a new avenue,” said Yakeel Quiroz, a neuropsychologist at Massachusetts General Hospital who helped lead the study published Wednesday. “There are definitely opportunities to copy or mimic effects.”
The first hints of this genetic protection appeared several years ago. Researchers were doing a huge amount of research. family in colombia A woman escapes her genetic fate when she discovers she shares a devastating inherited form of Alzheimer's disease. Aliria Piedrahita de Villegas should have developed Alzheimer's symptoms in her 40s, but she was well into her 70s before experiencing mild symptoms. cognitive impairment.
A key clue is that she is carrying something incredibly rare: two copies of an unrelated gene called APOE3 with a mutation called Christchurch. That strange pair of genes in hers seemed to protect her and stop her. genetic Predisposition to Alzheimer's.
Quiroz's team tested a large family of more than 1,000 people and identified 27 people who had a single copy of the Christchurch variant.
But is just one copy enough to provide protection? People from Christchurch showed the first signs of cognitive impairment at age 52, on average five years later than their relatives, according to a collaboration involving Brigham General researchers and the University of Antioquia, Colombia.
The findings, published in the New England Journal of Medicine, are encouraging, said Dr. Eliezer Masliah of the National Institute on Aging.
“It gives us a lot of comfort to know that modifying one of the copies may at least help delay the disease,” he said.
Some early studies have already begun to explore whether certain treatments can induce protective mutations, he added.
More than 6 million Americans, and about 55 million people worldwide, have Alzheimer's disease. Less than 1% of cases are like the one in the Colombian family. caused by genes After such generations causes disease At an unusually young age.
Alzheimer's disease is a disease that typically affects people over the age of 65, and while simply getting older is the main risk, the APOE gene has been known for a long time. play a role. There are three main varieties: Having one copy of the infamous APOE4 gene increases your risk, and a recent study found that having two copies of APOE4 may actually cause Alzheimer's disease in older people. Another variant, APOE2, appears to reduce risk, while APOE3 has long been considered neutral.
The seemingly protective role of the Christchurch variant was then discovered.
Silent changes in the brain appear at least 20 years before Alzheimer's symptoms appear. This involves the buildup of a sticky protein called amyloid. Amyloid appears to cause tangles of another protein called tau, which kills brain cells when it reaches certain levels. Previous research suggested that something about the Christchurch variant disrupts tau conversion.
Wednesday's study included brain scans of two people and analysis of autopsies of four other people who died, along with a copy of the Christchurch copy. Quiroz said there is still a lot to learn about how rare variants affect the underlying Alzheimer's disease process, including whether they affect the common older type, but tau and inflammation are among the suspects.