COLUMBIA (US) — African Americans with a specific gene variant have almost double the risk of developing late-onset Alzheimer’s disease compared with African Americans who lack the variant.
The ABCA7 gene is involved in the production of cholesterol and lipids, which suggests that lipid metabolism may be a more important pathway in Alzheimer’s disease in African Americans than in whites.
Because cholesterol and lipid imbalances (which eventually lead to vascular disease and heart attacks and strokes) are more common in African Americans, treatments that reduce cholesterol and vascular disease may potentially be an effective way to reduce or delay Alzheimer’s in this population.
“Our findings strongly suggest that ABCA7 is a definitive genetic risk factor for Alzheimer’s disease among African Americans,” says study senior author, Richard Mayeux, professor and chair of neurology at Columbia University Medical Center. “Until now, data on the genetics of Alzheimer’s in this patient population have been extremely limited.
“While we need to conduct research to determine whether reducing cholesterol will lower the chance of Alzheimer’s in African Americans, maintaining healthy cholesterol levels always has the benefit of lowering one’s risk of heart attack and stroke.”
Published in the Journal of the American Medical Association, the study involved nearly 6,000 African American participants, most of whom are volunteers from 18 NIH-funded Alzheimer’s Disease Centers.
The purpose of the study was to look for genetic variants among African-Americans, who are known to have a higher incidence of late-onset Alzheimer’s than whites living in the same community. Ninety percent of all cases of Alzheimer’s, which affect an estimated 5 million Americans aged 65 and older, are described as having the late-onset form of the disease.
“ABCA7 is the first major gene implicated in late-onset Alzheimer’s among African Americans, and it has an effect on disease risk comparable to that of APOE-e4—which has been known for two decades to be a major genetic risk factor in whites,” says Christiane Reitz, assistant professor of neurology, who conducted the study’s genetic analyses as first author on the paper.
“Both genes raise the risk of Alzheimer’s in this population twofold.” The extent of the role of APOE-e4 in African Americans had been uncertain because of inconsistent results from previous, smaller studies.
“Based on these results, we now know that both APOE-e4 and ABCA7 are major genetic risk factors for African Americans, whereas for whites, only one of the two—APOE-e4—confers a similar degree of risk,” Mayeux says.
Several other genes that had recently been linked to Alzheimer’s in white populations were also confirmed in the current study to play a role in African Americans.
“Because they cross ethnic groups, the likelihood increases that these genes are very important in the development of Alzheimer’s,” Reitz says. “And that gives us clues in our search for the cellular pathways associated with the disease.”
Genetic underpinnings vary
“These findings suggest that the genetic underpinnings of Alzheimer’s disease may vary among different populations—and so should not be treated homogeneously.”
“One of the key research goals set forth in the National Alzheimer’s Project Act of 2011 is to improve outcomes for ethnic and racial minority populations that are at higher risk for this devastating disease,” says Neil Buckholtz, of the National Institute on Aging. “These findings advance our understanding of genetic underpinnings that may play a role in disease onset and progression in African-Americans and suggest a novel target for therapeutic development.”
ABCA7 also affects the transport of several important proteins, including amyloid precursor protein, which is involved in the production of amyloid—the major source of the plaques that develop in the brains of Alzheimer’s patients. Thus, there are multiple ways that ABCA7 might contribute to an increased risk of late-onset Alzheimer’s disease among African Americans.
The most immediate impact of the new findings will be for scientists studying the causes of Alzheimer’s and ways to prevent the disease.
“Our next step is to do more lab work and more genetic sequencing, to understand the biological reasons for the increased risk seen with ABCA7 and other genes implicated in late-onset Alzheimer’s disease,” Mayeux says.
While the study’s discoveries may eventually lead to the development of genetic risk estimates specific to African Americans, Mayeux cautions that the utility of genetic testing for Alzheimer’s is still years away. “We are not yet at the point where we can take what we know about Alzheimer’s genes and come up with an accurate risk assessment.”
The study’s findings also must be replicated in independent groups of African Americans.
“The participant data pooled together for this analysis basically represented all of the African-American samples from well-characterized individuals in the United States,” Buckholtz says.
“Because large sample sizes are needed to conduct reliable genetic analyses, it is vitally important that African Americans and people of other racial/ethnic groups participate in genetic studies.”
Researchers from Boston University, University of Pennsylvania, University of Washington, Indiana University, Johns Hopkins University, University of Pittsburgh, Washington University in St. Louis, and Vanderbilt University also contributed to the study.
Source: Columbia University