African-Americans have a slightly higher risk of Alzheimer's disease than people of largely European ancestry, but there is no major genetic difference that could account for the slight excess risk, new research shows.
The results are from one of the only large studies ever done on Alzheimer's in African-Americans. Researchers identified the same gene variants in older African-Americans that they had found in older people of European ancestry. But they found that African-Americans with Alzheimer's disease were slightly more likely to have one gene, ABCA7, that is thought to confer risk for the disease.
Another gene, APoE4, long known to increase Alzheimer's risk in older white people, was present in about the same proportion of African-Americans with Alzheimer's as it is in people of European ancestry.
The researchers' paper was published online on Tuesday in The Journal of the American Medical Association. In an accompanying editorial, Dr. Robert L. Nussbaum of the University of California, San Francisco, noted that finding ABCA7 and APoE4 in African-Americans as well as those of European ancestry "strengthens the case" that the genes are important in conferring susceptibility to the disease.
John Hardy, an Alzheimer's researcher at University College London and a discoverer of the first gene mutation found to cause Alzheimer's, applauded the effort to study minorities. But, he said, because the data confirmed what was already known among those of European descent, "I don't think they tell us much new."
The data for the analysis came from nearly 6,000 African-Americans who were over age 60 and had participated in studies at 18 medical centers. About 2,000 had Alzheimer's disease, and the rest, for comparison, did not. Dr. Richard Mayeux of Columbia University was the lead author of the study.
The researchers calculated that ABCA7 increased Alzheimer's risk by about 80 percent in African-Americans, compared with about 10 percent to 20 percent in people of European ancestry. Those are considered modest increases; a gene that carries a significant risk would increase the chances of getting a disease by well over 200 percent. And ABCA7 was not very common, still leaving most Alzheimer's risk unexplained. About 9 of every 100 African-Americans with Alzheimer's had the gene, compared with 6 out of 100 who did not have the disease.
Dr. Hardy cautioned that the difference in risk between African-Americans and those of European ancestry who had ABCA7 was unlikely to be meaningful. It is to be expected that genetic links that are tenuous, like that with ABCA7, would be more significant in some studies and less in others, simply because populations, purely by chance, would vary slightly, he explained.
Even before this study, researchers had been working on the assumption that ABCA7 has something to do with Alzheimer's disease. The gene is involved in facilitating the movement of cholesterol in and out of cells and is thought to play a role in the development of heart disease, too. That suggests, Dr. Mayeux said, that it might not be coincidence that many people get both Alzheimer's and cardiovascular disease.
ABCA7 also moves proteins through the membranes that encase cells. One of the proteins it transports is a precursor of beta amyloid, the major component in the brain plaques found in Alzheimer's disease. In studies with mice, Dr. Mayeux said, disabling ABCA7 results in an accumulation of amyloid in the brain.
But, he said, the gene's function is not well understood. "We don't know the mechanism for amyloid accumulation," Dr. Mayeux said. The current understanding of ABCA7 "is just not there yet."
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