Family’s genes offer new clue to delaying onset of Alzheimer’s disease

Scientists who studied a family plagued by Alzheimer’s disease early in life found that some carry a genetic oddity that delays initial symptoms by five years.

The discovery points to new ways to combat the mind-stealing disease – if researchers can figure out how a single copy of this very rare genetic variant offers at least a little protection.

“This breaks new ground,” said neuropsychologist Yakeel Quiroz of Massachusetts General Hospital, who helped lead the study published Wednesday. “There are definitely opportunities to copy or imitate the effects.”

The first indication of this genetic protection emerged a few years ago. Researchers were studying a huge family in Colombia who shares a devastating hereditary form of Alzheimer’s when they discovered a woman who escaped her genetic destiny. Aliria Piedrahita de Villegas should have developed symptoms of Alzheimer’s at age 40, but instead reached age 70 before suffering even a mild form of Alzheimer’s disease. cognitive problem.

The big clue: She also harbored something incredibly rare, two copies of an unrelated gene called APOE3 that had a mutation called Christchurch. This strange pair of genes seemed to protect her, keeping her away genetic predisposition to Alzheimer’s.

Quiroz’s team then tested more than 1,000 relatives and identified 27 who carried a single copy of the Christchurch variant.

But would a copy be enough to offer some protection? Christchurch sufferers showed, on average, the first signs of cognitive problems at age 52, five years after their family members, concluded a collaboration that includes researchers from Mass General Brigham and Colombia’s Antioquia University.

The findings, published in the New England Journal of Medicine, are encouraging, said Dr. Eliezer Masliah of the National Institute on Aging.

“It’s very reassuring to know that modifying one of the copies could be really useful,” at least in helping to slow the disease, he said.

Some early work is already beginning to explore whether certain treatments can induce the protective mutation, he added.

More than 6 million Americans and about 55 million people worldwide have Alzheimer’s. Less than 1% of cases are like those in the Colombian family, caused by a gene passed through generations that triggers the disease at exceptionally young ages.

Alzheimer’s disease is generally a disease of people over the age of 65, and although simple aging is the main risk, it has long been known that the APOE gene play some role. It comes in three main varieties. Carrying one copy of the notorious APOE4 gene increases your risk – and recent research has found that having two copies of APOE4 can actually cause Alzheimer’s in the elderly. Another variety, APOE2, appears to reduce risk, while APOE3 has long been considered neutral.

Then came the discovery of the Christchurch variant’s apparently protective role.

Silent changes in the brain precede Alzheimer’s symptoms by at least two decades — including the buildup of a sticky protein called amyloid that, once it reaches certain levels, appears to trigger tangles of another protein, called tau, that kill brain cells. Previous research has suggested that something about the Christchurch variant impedes tau transition.

Wednesday’s study included brain scans of two people with a single Christchurch copy and autopsy analysis of four other people who died. Quiroz cautioned that there is still much to learn about how the rare variant affects the underlying process of Alzheimer’s — including whether it affects the common type of old age — but said tau and inflammation are among the suspects.