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Does ApoE4 Mean Alzheimer’s? Not For Everyone

By Simon Spichak, MSc | March 31st, 2022

ApoE4 has long been understood to boost Alzheimer’s risk. For the first time, scientists studied this Alzheimer’s risk factor gene in the American Indian population. The results raise more questions than they answer.

Ask most anyone involved in Alzheimer’s research what the disease’s strongest genetic risk factor is, and there will be no debate: the the E4 variant of apolipoprotein E, also known as ApoE4. In white people, ApoE4 is known to the risk of Alzheimer’s by a factor of 12. But in people of color, this gene — and Alzheimer’s in general — appears to be a whole different story. 

Part of the problem is that Alzheimer’s research, including drug trials, has historically been overwhelmingly white. A lack of diversity among study participants means that, relatively speaking, there is very little data about how Alzheimer’s develops in populations of color, and to what extent treatments are effective. 

A new study in Alzheimer’s & Dementia looked at carriers of the ApoE4 gene in the American Indian population. What they found was surprising: Their study did not find evidence that ApoE4 increased carriers’ risk of Alzheimer’s at all. 

Does ApoE4 Mean You’ll Develop Alzheimer’s?

Researchers recruited 811 individuals between the ages of 64 and 95 who underwent cognitive testing and brain imaging. Comparing carriers to non-carriers, they found no differences in brain volume or cognitive performance. The study could not establish any associations between ApoE4, neurodegeneration, and cognitive impairment in this population. 

The study was led by Astrid M. Suchy-Dicey, an assistant professor at the Elson S Floyd College of Medicine at Washington State University. “It’s a little hard to understand why a biological effect from a gene would have a different association in other populations,” Suchy-Dicey told Being Patient, On a molecular level, Suchy-Dicey added, the gene functions  in the same way, regardless of ethnicity.  

“It’s probably a difference in some other aspect of the data,” Suchey-Dicey said, adding that other confounds or interactions with the environment may explain the differences. “This is similar to what has been found in African Americans and Hispanic Latinos.”

Why Is Alzheimer’s Risk Different Among People of Color?

There are a lot of other unknowns since the American Indian population along with other populations of color aren’t well-represented in Alzheimer’s studies, if at all. 

“We make a lot of assumptions on the basis of data and results found in non-Hispanic white people and also in men,” Suchey-Dicey said. “I think, historically, that has maybe been an aspect of convenience and availability, but to the detriment of our understanding of disease and all people.”

Even participation in these studies is difficult. Some people in rural communities needed to travel four to five hours by car to reach a research center in order to participate in Suchey-Dicey’s team’s American Indian study. Car ownership and other factors around access can be barriers to participation, making the lack of diversity in Alzheimer’s research a difficult challenge to address.

Cognitive tests are also an issue: These tests, currently the go-to for diagnosing Alzheimer’s and dementia, are racially biased. This bias makes it difficult to interpret the results. 

What We Still Don’t Know

Because American Indians are under-represented in Alzheimer’s research, it is unclear how their Alzheimer’s risk measures up to other racial groups.

“Our next step is to try to understand and measure the frequency of Alzheimer’s in this group,” Suchey-Dicey said. “It requires us to look at each individual participant’s data, one by one, with a panel of experts to come up to a consensus of [Alzheimer’s] status.” 

Studying these populations is hard work, requiring the researchers to build trust with the community. Suchey-Dicey explained that American Indians are involved within the research in roles as partners, beyond just being passive participants. Other programs are also teaching American Indians about Alzheimer’s in their own communities, including the NW Heron program at Washington State University.

These programs exist because better inclusion of American Indians in clinical trials will not only help determine why this study did not find an association between Alzheimer’s and ApoE4 — it will also bring us a more complete understanding of the disease.

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