Published April 10 in the prestigious Journal of the American Medical Association, their study, “Variants in the ATP-binding cassette transporter, ABCA7, and the apolipoprotein E ε4 allele substantially and equally influence risk of late-onset Alzheimer’s disease in African Americans,” provides new directions for biological, genetic and therapeutic studies of Alzheimer’s disease.
Margaret A. Pericak-Vance, Ph.D., director of the John P. Hussman Institute for Human Genomics and one of the senior authors, leads the analysis group for the Alzheimer’s Disease Genetics Consortium, which is responsible for the paper. The research is believed to be the largest genome-wide association study conducted on late-onset Alzheimer’s disease in African Americans, and includes 1,968 African American individuals with Alzheimer’s disease and 3,928 individuals without, whose cases were collected from multiple sites between 1989 and 2011.
“It is critical to identify and assess genetic contributions to Alzheimer’s disease in all populations,” said Pericak-Vance, who has researched the genetics of Alzheimer’s for decades. “Health disparities have had an especially profound effect on the overall health of African Americans in the United States and, although Alzheimer’s occurs as frequently in African Americans as other populations, there have been significantly fewer studies that include this population. This research will enable African Americans to take full advantage of the benefits of genomic medicine when research findings are translated into clinical practice.”
Pericak-Vance’s 1993 Science paper was the first to identify a form of the apolipoprotein E gene (APOE ε4), a gene involved in lipid metabolism, as a risk variant in Alzheimer’s disease. It accounts for more than 40 percent of all cases of Alzheimer’s, and remains the largest overall predictor for the disease. The paper continues to be one of the most-cited in all biomedical research.
While the latest paper confirms that APOE ε4 is the strongest risk factor for Alzheimer’s in African Americans, it also found that ABCA7, a gene likewise involved in lipid metabolism, is the second highest contributing risk factor in late-onset Alzheimer’s disease in African Americans. ABCA7 had previously been found to contribute to Alzheimer’s disease risk in non-Hispanic whites, but with a small effect. The paper showed that ABCA7 is associated almost as strongly in African Americans as APOE ε4 is in non-Hispanic whites.
These findings suggest that lipid metabolism is an important pathway of late-onset Alzheimer’s disease in African Americans. Understanding the etiology of Alzheimer’s disease will have a significant impact on future disease management.
Other lead institutions on the study are Columbia University, University of Pennsylvania, Boston University and Vanderbilt University. Other co-authors from the Hussman Institute are Gary Beecham, Ph.D., assistant professor of human genetics; Eden R. Martin, Ph.D., professor of human genetics; John R. Gilbert, Ph.D., professor of human genetics; and Kara Hamilton-Nelson, M.S., project manager for research support. Other Miller School co-authors include Deborah Mash, Ph.D., professor of neurology and Director of the University of Miami Brain Endowment Bank; Clinton B. Wright, M.D., M.S., associate professor of neurology and Scientific Director of the Evelyn F. McKnight Brain Institute; Regina M. Carney, M.D., assistant professor of psychiatry and behavioral sciences; and Elizabeth Crocco, M.D., assistant professor of psychiatry and behavioral sciences.
Pericak-Vance and her research team have been studying the genetics of Alzheimer’s disease in people of African American heritage for over a decade. Institute staff help educate diverse ethnic communities about what Alzheimer’s disease is and the warning signs and symptoms related to the disease. Additionally, through the Institute’s Genetics Awareness Project, faculty and staff have been reaching out to members of diverse ethnic communities to bring awareness about genetics research at UM. The work has included a multifaceted media campaign, outreach activities, and large educational events, including the second annual “Why We Can’t Wait: Conference to Eliminate Health Disparities in Genomic Medicine,” which will be held May 29-31 in San Francisco.
In 2010, the South Florida Business Journal recognized the Genetics Awareness Project with its Excellence in Health Care Award.
University of Miami,