Scientists Identify Rare Gene Mutation that Protects Against Alzheimer’s

A rare gene variant appears to protect against the degenerative brain disease, holding hope as a target for future drug development

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After years of studying genes that increase risk for Alzheimer’s disease, scientists report the promising discovery of DNA that does the opposite: the first gene variant that protects people against the neurodegenerative disorder.

The gene variant is rare — most people who do not have Alzheimer’s don’t have the mutation — but its function bolsters the theory that Alzheimer’s is caused by the accumulation of beta amyloid protein in the brain. The discovery also offers a potential new target for Alzheimer’s drugs and lends hope that the amyloid-targeting drugs that are currently in development may someday successfully prevent or slow the disease.

The newly identified variant affects a gene called APP, which encodes for the precursor protein that gets chopped up by enzymes and forms beta amyloid. The mutation seems to muddle the ability of one of the enzymes to do its job, therefore resulting in less amyloid production and a lower risk of Alzheimer’s. In the new study, people who lived to age 85 or older without developing Alzheimer’s were more than five times more likely to have the protective gene mutation than those who developed the disease — that translates to a 7.5 times lower risk of Alzheimer’s attributable to the variant. Based on cell culture studies, the scientists say the DNA change resulted in a 40% drop in amyloid production.

(MORE: U.S. Launches National Alzheimer’s Plan)

The gene also appeared to protect against a known risk factor for Alzheimer’s, the presence of two copies of another gene known as ApoE4. At least 90% of people with two copies of this gene develop Alzheimer’s by age 80, but among the 25 people in the study who had two copies of ApoE4 and the new protective variant, none had Alzheimer’s. Further, the presence of the new gene variant seemed to protect against memory loss and cognitive decline even in people who didn’t have Alzheimer’s. When the researchers looked at elderly people with normal brain function, they found that those with the new APP gene mutation did better on cognitive tests than those without.

More than 30 variants of the APP gene have been identified in the past — about 25 of them detrimental. Many such changes boost production of beta amyloid and lead to an early-onset form of Alzheimer’s that affects people before age 65, many in their 30s or 40s. The new APP variant, reported in the journal Nature by researchers led by Kari Stefansson, founder of deCODE Genetics in Iceland, is the first to convey a protective effect.

For their study, Stefansson and her colleagues analyzed the entire genomes of 1,795 Icelanders, looking for protective variants of APP. The one that stood out when the researchers compared people with Alzheimer’s with a control group that did not, was rare overall — present in only about 0.45% of people in Iceland. The study data showed that 0.13% of people over age 85 with Alzheimer’s had the variant, compared with 0.62% of those who did not have the disease. The mutation was also found in 0.79% of people over 85 with normal brain function.

(MORE: New Criteria May Change Alzheimer’s Diagnosis)

Not only are the findings encouraging for finding new treatment strategies, but they also help solidify researchers’ understanding of what drives the memory-robbing disease. For years, experts have believed that beta amyloid buildup was the primary cause of the nerve death and the cognitive decline associated with Alzheimer’s, but that theory has been called into question. For starters, evidence from autopsies of the brain showed that many elderly people remain intellectually intact despite having amyloid deposits in their brain. Confusing things even further was the fact that clinical trials of numerous drug treatments and a vaccine designed to decrease the amyloid burden in Alzheimer’s patients have all failed to alleviate the symptoms of memory loss, cognitive decline and confusion that characterize the disease.

Researchers began to wonder whether beta amyloid was really driving Alzheimer’s, or whether it was merely a byproduct of some other process causing degeneration or part of the brain’s response to damage itself. However, advanced imaging studies have added evidence that beta amyloid burden does indeed play a critical role in accelerating Alzheimer’s — but they suggest that the problem may lie not with overproduction of the protein, but with a failure in the brain’s ability to clear it away efficiently.

Many experts also think the experimental anti-amyloid drug treatments failed because they were administered too late, after damage in the brain had become irreversible. An upcoming trial will test whether giving drugs early to people who carry risk genes for Alzheimer’s, before they develop symptoms, can stave off the disease. Stefansson’s study offers confidence that such ongoing research is on the right path.

(MORE: New Drug Trial Aims to Prevent Alzheimer’s Before It Starts)

The study also reveals another target for pharmaceutical companies to pursue, and the authors predict that drug makers will try to create treatments that mimic the new APP gene variant’s effects. It’s only a first step, but knowing that there may be protective genes as well as pathogenic ones in Alzheimer’s offers hope for the 5.4 million currently affected.

Alice Park is a writer at TIME. Find her on Twitter at @aliceparkny. You can also continue the discussion on TIME’s Facebook page and on Twitter at @TIME.

Samantha Kennedy
Samantha Kennedy

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 ”More than 5 million Americans are living with Alzheimer’s disease. On Tuesday, the Obama Administration announced the launch of the National Alzheimer’s Plan, with the goal of finding effective ways to prevent and treat the devastating effects of dementia by 2025.” Time Magazine

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As Dr. Caldwell Esselstyn ( has shown with hundreds of heart disease patients, you can preserve or repair your blood vessel walls by eating a plant-based diet that’s high in the building blocks of nitric oxide: leafy greens, legumes, oats amp; beans.

Exercise also stimulates the endothelium (blood vessel linings) to produce more nitric oxide.

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Ian Welch


I work with a lot of clients who have early stage Alzheimer's Disease. It is devistating to see once articulate people become dependent. I try to keep things as simple as possible with lots of reminder notes and visual cues.


Helpful Resource for Caregivers: