Sunday, April 14, 2013

A variation in the gene ABCA7 causes the risk of late-onset Alzheimer's disease to double in African-Americans

The research, the largest analysis yet to establish genetic risk linked to late-onset Azheimer's disease in African-Americans, was undertaken by the Alzheimer's Disease Genetics Consortium and led by scientists 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 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 plays a part in the production of lipids and cholesterol, which indicates that lipid metabolism might be a more crucial pathway for the disease in African-American individuals than in whites. It is more common for African-Americans to experience lipid and cholesterol imbalances - which ultimately result in heart attacks, strokes, and vascular disease. Therefore, the researchers explained that treatments that lower cholesterol and vascular disease could possibly be a successful way to decrease or delay Alzheimer's among this group of people. The experts aimed to look for genetic variants in African-Americans, who generally have an increased incidence of late-onset Alzheimer's, compared to whites residing in the same community. Alzheimer's affects approximately 5 million people aged 65 and older in the United States, and 90% of all cases of the disease are reported to be the late-onset form. Christiane Reitz, MD, PhD, first author and assistant professor of neurology, said: "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. Both genes raise the risk of Alzheimer's in this population twofold." The importance of the role of APOE-e4 in African-Americans had been unclear due to conflicting results from prior, smaller investigations. "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," said Dr. Mayeux, who is also co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H. Sergievsky Center at CUMC. Many other genes that had recently been associated with the disease in white people were also shown in this report to have a role in African-Americans. Dr. Reitz, who is a member of both the Sergievsky Center and the Taub Institute, explained: "Because they cross ethnic groups, the likelihood increases that these genes are very important in the development of Alzheimer's. And that gives us clues in our search for the cellular pathways associated with the disease. These findings suggest that the genetic underpinnings of Alzheimer's disease may vary among different populations - and so should not be treated homogeneously."

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