A new study has revealed that a gene that was once thought to be weakly associated with Alzheimer's disease risk in white people may almost double the risk of developing the debilitating neurological disease when it's present in African-Americans.
Researchers analyzed data on nearly 6,000 African-Americans for the study, which was published April 10 in the Journal of the American Medical Association (JAMA).
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They were looking for genes that were associated with late-onset Alzheimer's disease, the most common cause of dementia. About 1 percent of adults age 65 are diagnosed with Alzheimer's, according to the researchers, but more than 30 percent of people older than 80 receive the diagnosis.
African-Americans in particular have higher incidence rates of late-onset Alzheimer's compared to white people living in the same community, the researchers added. They hoped if they found a genetic variant linked to disease risk in African-American patients, they can one day identify targets for genetic testing or find out ways to prevent or treat the degenerative disease.
The researchers compared data on about 1,970 African-American Americans with Alzheimer's with data on more than 3,900 healthy counterparts who served as control subjects. All data was collected between 1989 and 2011, and genetic information was assessed based on patient cases and family-based data sets.
African-Americans who had the ABCA7 gene were about 1.8 times more likely to develop late-onset Alzheimer's than those who didn't have the gene. Those who had the APOE gene -- which has previously been associated with increased risk for the disease among white people of European ancestries -- were 2.3 times more likely to develop Alzheimer's than those without the APOE-e4 genotype.
The association between disease risk and the ABCA7 gene was 60 percent stronger than the link observed among white people who had the gene.
ABCA7 affects the transport of certain proteins in the brain, including amyloid precursor protein, according to the researchers. That protein is used for the production of amyloid, the plaque substance that develops in the brains of people with Alzheimer's.
"Our findings strongly suggest that ABCA7 is a definitive genetic risk factor for Alzheimer's disease among African-Americans," senior study author Dr. Richard Mayeux, professor and chair of neurology at Columbia University Medical Center in New York City, said in a press release. "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."
The link between Alzheimer's risk and the APOE gene in people of European ancestry has been known for about 20 years, according to the researchers.
"While the genotypes are similar between groups, the strength of risk is significantly different," study co-author Dr. Gerard Schellenberg, a professor of pathology and laboratory medicine at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, said in a press release. "ABCA7 was previously identified to be weakly involved in the risk of Alzheimer disease among non-hispanics of European ancestry. Among African Americans, however, the gene is associated with a much stronger risk of late-onset Alzheimer disease."
Dr. Christiane Reitz, assistant professor of neurology at Columbia who conducted the genetic analysis, said of the new study, "these findings suggest that the genetic underpinnings of Alzheimer's disease may vary among different populations -- and so should not be treated homogeneously."
"This is a major finding because it shows that blacks have an additional risk factor compared to whites,'' Dr. Neil Buckholtz, director of neuroscience at the National Institute on Aging, commented to USA Today. His agency is part of the National Institutes of Health, which funded the study. "It's a highly significant risk that doesn't exist in other populations. In order to find interventions, we need to explore all the various risks."
The findings are significant given only a small fraction of genome studies look at African American populations, Dr. Robert Nussbaum, chief of the division of medical ethics at the University of California, San Francisco, wrote in an accompanying editorial published in the same journal issue.
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"Pursuing research in an understudied ethnic group is important for scientific and for ethical reasons," he wrote.
He noted that the findings need to replicated or more studies to strengthen the case that these genetic variants are important predictors of disease.
About 5.2 million Americans have Alzheimer's or some other form of dementia, rates that are expected to rise to 13.8 million by 2050. A recent report from the Alzheimer's Association found one in three adults die with Alzheimer's or some type of dementia.
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