Colombian family's genes offer new clues to delaying Alzheimer's disease

Washington — Scientists studying families affected by early-onset Alzheimer's disease have discovered that some members carry a genetic abnormality that delays the onset of early symptoms by five years.

The discovery points to a new way to fight the mind-destroying disease: If researchers can figure out how one copy of the gene works, Very rare genetic mutation It offers at least a little protection.

“This opens up new avenues,” said Yakiel Quiroz, a neuropsychologist at Massachusetts General Hospital who led the study published Wednesday. “There's definitely an opportunity to mimic or replicate that effect.”

The first hints of this genetic protection appeared a few years ago, when researchers were studying a large Colombian family that shared a devastating hereditary form of Alzheimer's disease and discovered one woman who had escaped that genetic fate: Aliria Piedrahita de Villegas, who should have developed symptoms of Alzheimer's in her 40s, had survived into her 70s without suffering even mild cognitive impairment.

A big clue was that she also had something very unusual: two copies of an unrelated gene, APOE3, that had a mutation called Christchurch. This odd genetic combination seemed to protect her, warding off a genetic predisposition to Alzheimer's.

Quiroz's team then tested more than 1,000 relatives and identified 27 people who carried one copy of the Christchurch variant.

But does one copy offer any protective effect? ​​Christchurch carriers showed the first signs of cognitive impairment at age 52, five years later on average than their relatives, concluded a collaborative study including researchers at Massachusetts General Hospital's Brigham Research Institute and the University of Antioquia in Colombia.

Dr Eliezer Masria of the National Institute on Aging said the findings of the study, published in the New England Journal of Medicine, were encouraging.

“It's very reassuring to think that correcting one of the copies could be very helpful in at least slowing the progression of the disease,” he said.

He added that very early studies have already begun to test whether certain treatments induce protective mutations.

Alzheimer's affects more than 6 million people in the United States and an estimated 55 million people worldwide. In fewer than 1% of cases, like the Colombian family's, a gene passed down through generations causes the disease at an unusually young age.

Alzheimer's is a disease that usually affects people over 65, and while age is the main risk, it has long been known that the APOE gene plays a role. There are three main types of APOE genes. Having one copy of the infamous APOE4 gene increases your risk. Recent studies have shown that having two copies of APOE4 can actually Causes Alzheimer's disease in the elderlyAnother type, APOE2, appears to reduce risk, while APOE3 has long been thought to be neutral.

It was subsequently discovered that the Christchurch variant appears to play a protective role.

Tranquility Brain changes precede Alzheimer's symptoms It takes at least 20 years for the sticky protein known as amyloid to build up. When it reaches a certain level, it's thought to trigger tangles of another protein called tau, which kills brain cells. Previous research has suggested that something in the Christchurch variant prevents tau from migrating.

Wednesday's study included brain scans from two people with one copy of the Christchurch gene, as well as autopsy results from four others who died. Quiroz cautioned that there was still much to be learned about how the rare mutation affects the underlying process of Alzheimer's, including whether it affects the more common, older-ageing form, but said tau protein and inflammation were one cause.

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