Researchers Discover Gene That Doubles Alzheimer's Risk In African-Americans
April 10, 2013

Researchers Discover Gene Mutation That Doubles Alzheimer’s Risk In African-Americans

Lawrence LeBlond for - Your Universe Online

Researchers reporting in Tuesday´s issue of JAMA have identified a new gene mutation that nearly doubles the risk of developing Alzheimer´s disease in older blacks. The findings come from the largest genome-wide, government-funded study on Alzheimer´s genes in the African-American community.

The mutation found in gene ABCA7 is not the first linked to the cognitive disease but does come as a significant breakthrough in Alzheimer´s research, suggesting there could be multiple causes of the disease and therefore ways to treat it, according to researchers.

The ABCA7 gene is also linked to Alzheimer´s in whites, but does not appear to show as much of a risk in that race as it does in blacks. And while a doubling up on the risk factor may sound large, the team of researchers stressed that it is only a modest increase. They say risk of Alzheimer´s in older adults could depend on a number of factors — not only genes, but also environmental influences.

The study was conducted by the Alzheimer´s Disease Genetics Consortium and was led by neurologists from Columbia University Medical Center (CUMC). The study received primary funding from the National Institutes of Health (NIH), with additional funding from the Alzheimer´s Association and GlaxoSmithKline.

Senior author Richard Mayeux, MD, MS, professor of neurology at CUMC, said the study findings “strongly suggest that ABCA7 is a definitive genetic risk factor for Alzheimer´s disease among African-Americans“¦ Until now, data on the genetics of Alzheimer's in this patient population have been extremely limited."

The gene, which is involved in cholesterol and lipid production, may reveal that lipid metabolism is a more important pathway in development of Alzheimer´s in blacks than in whites. Because cholesterol and lipid imbalances are more common in African-Americans, treatments that reduce cholesterol and onset of vascular disease may potentially prove effective in reducing or delaying Alzheimer´s.

"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 in a statement.

For the study, Mayeux and colleagues analyzed samples from nearly 6,000 African-American men and women, most of whom are volunteers from 18 NIH-funded Alzheimer´s Disease Centers. The samples were contributed to a research program led by Gerard D. Schellenberg, PhD, at the University of Pennsylvania (UPenn).

Of the 6,000 volunteers, about a third (nearly 2,000) were diagnosed with probable Alzheimer´s; the remaining group was cognitively normal. African-Americans are known to have a higher incidence of late-onset Alzheimer´s than their white counterparts found in the same community. And 90 percent of all cases of the cognitive-robbing disease affects those aged 65 and older, 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," said first author Christiane Reitz, MD, PhD, assistant professor of neurology, who conducted the study's genetic analysis. "Both genes raise the risk of Alzheimer's in this population twofold."

Previous studies have shown inconsistencies in the extent of the role of APOE-e4 in African-Americans.

But in the new study, the researchers have painted a clearer picture of the role both APOE-e4 and ABCA7 have in Alzheimer´s risk in African-Americans. As for whites, only the APOE-e4 gene results in a similar risk of developing Alzheimer´s, according to Dr. Mayeux.

Other genes have also in past studies been linked to Alzheimer´s in white populations, and the new study was able to confirm those links as well in the African-American population.

The study findings suggest that the genes play an important role in the development of Alzheimer´s, and can offer clues in the hunt for cellular pathways that are also associated with the disease, according to Dr. Reitz.

"These findings suggest that the genetic underpinnings of Alzheimer's disease may vary among different populations–and so should not be treated homogeneously," added Dr. Reitz.

The researchers also noted that the ABCA7 gene affects the transport of several important proteins, including amyloid precursor protein, which is involved in amyloid production, a major source of plaque that develops in the brains of Alzheimer´s patients. This is one of several factors that could lead to an increased risk of late-onset Alzheimer´s in the black community.

The researchers said the findings could open doors in the search for 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," said Dr. Mayeux.

While the results of this study could eventually lead to developments in genetic risk estimates specific to African-Americans, Dr. Mayeux said that such genetic testing is likely still years out. "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," he said.

Dr. Mayeux also explained that the study findings 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," said Dr. Neil Buckholtz, PhD, of the National Institute on Aging, which leads the NIH effort to find ways to treat, delay or prevent Alzheimer's.

"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 supported by NIA," he added.

Buckholtz noted that such studies are made possible through collaboration and data-sharing efforts among researchers.