Colombian family’s genes offer new key to delaying Alzheimer’s disease

Scientists studying a family affected by early-onset Alzheimer’s disease have discovered that some of its members carry a genetic rarity that delays the onset of symptoms by five years.

The discovery points to new ways to combat the disease if researchers can figure out how a single copy of this rare genetic variant provides even a modicum of protection.

“This opens up new possibilities,” says neuropsychologist Yakiel Quiroz of Massachusetts General Hospital, who helped lead the study published Wednesday. “There are definitely opportunities to copy or imitate the effects.”

The first signs of such genetic protection appeared several years ago. Researchers were studying a large Colombian family suffering from a devastating, inherited form of Alzheimer’s disease when they discovered a woman who had escaped her genetic fate. Aliria Piedrajita de Villegas should have started to show symptoms of Alzheimer’s disease at age 40, but reached age 70 before developing mild cognitive problems.

Big clue: Piedrajita de Villegas also contained something incredibly rare: two copies of an unrelated gene called APOE3, a mutation of which was named Christchurch. This odd pair of genes seemed to protect her, keeping her genetic predisposition to Alzheimer’s disease at bay.

Quiros’ team then analyzed more than 1,000 family members and identified 27 carriers of a single copy of the Christchurch variant.

But will a copy be enough to provide any protection? Carriers of the disease in Christchurch first showed signs of cognitive problems at an average age of 52, five years later than their relatives, concluded researchers from the Mass General Brigham hospital system and the University of Antioquia in Colombia.

The results, published in the New England Journal of Medicine, are encouraging, according to Dr. Eliezer Maslia of the National Institute on Aging.

More than 6 million Americans and about 55 million people worldwide have Alzheimer’s disease. Less than 1% of cases are similar to the case in the Colombian family and are caused by a gene passed down through generations that causes the disease at an unusually early age.

Alzheimer’s disease usually affects people over 65, and while the main risk factor is simply aging, the APOE gene has long been known to play a role. It comes in three main varieties. Carrying one copy of the famous APOE4 gene increases your risk, and recent studies have shown that having two copies of APOE4 can cause Alzheimer’s disease in older people. Another variant, APOE2, appears to reduce risk, while APOE3 has long been considered neutral.

The apparent protective role of the Christchurch variant was then discovered.

Silent changes in the brain precede symptoms of Alzheimer’s disease by at least two decades, including the buildup of a sticky protein called amyloid that, once it reaches a certain level, appears to trigger a tangle of another protein called tau that kills brain cells . Previous studies have shown that the Christchurch variant prevents this transition to tau.

Wednesday’s study included brain scans of two single-copy individuals from Christchurch and analysis of post-mortem examinations 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 disease (even if it affects the normal pattern of aging), but noted that tau and inflammation are among the suspected factors.


The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science Education Media Group. AP is solely responsible for all content.

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