African-Americans with a variant of the ABCA7 gene have almost double the risk of developing late-onset Alzheimer’s disease compared with African-Americans who lack the variant. The largest genome-wide search for Alzheimer’s genes in the African-American community, the study was undertaken by the Alzheimer’s Disease Genetics Consortium and led by neurologists from Columbia University Medical Center.
“Our findings strongly suggest that ABCA7 is a definitive genetic risk factor for Alzheimer’s disease among African-Americans,” said study senior author, Richard Mayeux, MD, MS, professor and chair of Neurology at CUMC. “Until now, data on the genetics of Alzheimer’s in this patient population have been extremely limited.”
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.
“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,” said Dr. Mayeux.
The study, published today in the Journal of the American Medical Association (JAMA), involved nearly 6,000 African-American participants, most of whom are volunteers from 18 NIH-funded Alzheimer’s Disease Centers. The Centers and other researchers contributed samples to the Alzheimer’s Disease Genetics Consortium, an NIH-supported research program led by Gerard D. Schellenberg, PhD, at the University of Pennsylvania. Approximately 2,000 of the volunteers were diagnosed with probable Alzheimer’s disease and 4,000 were cognitively normal. 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 Caucasians 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.
“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,” said Dr. Mayeux.
Several other genes that had recently been linked to Alzheimer’s in Caucasian 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,” said Christiane Reitz, MD, PhD, assistant professor of neurology, who conducted the study’s genetic analyses as first author on the paper. “And that gives us clues in our search for the cellular pathways associated with the disease.”
