There's Now a Better Genetic Predictor for Alzheimer's

Researchers have calculated the risk of being afflicted with Alzheimer's based on 32 DNA markers.

Scientists have come up with a way to translate your DNA into a potential risk factor for developing the most common form of dementia, late-onset Alzheimer’s.

As you might guess from its name, this form of dementia is very age-dependent. Our risk for developing the disease increases as we get older.

But not everyone has the same level of risk, and numerous studies (reviewed here) have shown that genetics plays a big role.

In a recent study published in PLOS Medicine, a group of researchers were able to identify the most telling DNA markers associated with late-onset Alzheimer’s.

A DNA marker is a location in someone’s DNA associated with a trait. The researchers, from the University of California, San Francisco, UC San Diego and other institutions, found multiple pieces of DNA associated with either an increased or decreased risk for late-onset Alzheimer's.

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The researchers compared the DNA of 17,008 people with and 37,154 people without Alzheimer's to create, for the first time, what's called a polygenic hazard score for late-onset Alzheimer's. This means they calculated the risk based on multiple DNA markers -- 32, to be exact -- rather than a single marker.

They then tested their new predictors on thousands of other Alzheimer’s patients as well as older people who did not have the disease, and found that the tool worked well for predicting when people of European descent would develop the disease.

While this method will not provide each person with a definitive answer as to their risk for late-onset Alzheimer's, it is the most promising predictor to date.

How the Science Works

The tool's risk estimate is derived from the sum of someone's DNA markers. So maybe you have an increased risk from marker 1, a decreased risk from marker 2, and so on.

Here’s what this might mean for a 65-year-old woman with no signs of dementia. According to the study, if she has a high-risk set of DNA with regard to late-onset Alzheimer’s, then she has around a 20 percent chance of developing the disease by age 85 and a whopping 90 percent chance by age 95.

If this same woman had been lucky enough to be born with a protective set of DNA, then her risk by age 85 would be less than 1 percent, and her risk by age 95 a bit under 3 percent.

These are the extremes. For the vast majority of people who reach age 65 without any symptoms, the range for getting late-onset Alzheimer’s by age 85 is 1.5 to 5 percent and by age 95,  6 to 22 percent.

Scientists have been relying on just a few DNA markers to estimate late-onset Alzheimer's risk. The most useful are the DNA markers in the APOE gene (APOE2, APOE3, and APOE4). These markers form the basis of the new FDA-approved, direct to consumer genetic test offered by 23andMe.

DNA is Not Destiny

It is important to keep in mind that none of this means someone will develop Alzheimer’s or be protected from it. These DNA markers just indicate someone is more or less likely to get Alzheimer’s. Even in the highest risk group, around 80 percent of those who do not get Alzheimer’s by age 65 still won’t have it by 85.

It is also important to note that in its current form, the researchers do not know how accurate this tool is for people who are not of European descent. There were not enough non-white people in the study to determine if the same DNA markers affect their risk similarly. Follow-up studies are needed to determine if this genetic predictor works for them or if it will need to be tweaked.

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Dr. Barry Starr is a scientist in the Department of Genetics at Stanford University. He runs the Stanford at The Tech program and the Understanding Genetics website with The Tech Museum of Innovation in San Jose, California. 

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