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Gene linked to higher Alzheimer's risk in blacks

Janice Lloyd, USA TODAY
  • This is the largest genome-wide study for Alzheimer%27s in African Americans
  • The ABCA7 gene is involved in the production of cholesterol and lipids
  • Genetic underpinnings for the disease may vary among populations
A new gene mutation is linked to a higher risk of late onset of Alzheimer's disease in African Americans, a study suggests.

A new gene mutation has been identified that nearly doubles African Americans' risk for getting Alzheimer's disease, according to a large, government-funded report out Tuesday.

The mutation in the gene ABCA7 is not the first linked to the disease but it is a major breakthrough in research, suggesting there could be multiple causes of Alzheimer's and therefore ways to treat the most common form of dementia, says the report, published Tuesday in the Journal of the American Medical Association.

There is no effective way to prevent, cure or delay Alzheimer's, a neurodegenerative illness that robs people of memory and other cognitive and emotional functions. The predominant late-onset form of Alzheimer's occurs after age 65 and is more common in blacks than whites. The study involved almost 6,000 black volunteers who had genetic testing; approximately 2,000 were diagnosed with probable Alzheimer's and 4,000 were cognitively normal.

"The first thing this tells us is there are probably many different ways to get Alzheimer's,'' says the study's senior author, Richard Mayeux, chair of the department of neurology at Columbia University Medical Center, New York. "It might be like some forms of cancer where the type of cancer you have dictates the type of treatment you receive."

The ABCA7 gene is involved in producing cholesterol and lipids, suggesting they may be a more important pathway in Alzheimer's disease in blacks than in whites, the authors say. High cholesterol and lipid levels can lead to vascular disease, heart attacks and strokes and are more common in blacks. Treatments that lower cholesterol and lipids may potentially be an effective way to reduce or delay Alzheimer's in patients with the gene variant, Mayeux says.

A variant, or mutation, is an abnormal change in the sequence of the chemicals inside a gene. Whites with the ABCA7 mutation are also at increased risk, but not as significantly as blacks, he adds.

Several gene mutations have been linked with increased Alzheimer's risk; the most significant in both whites and blacks has been APOE-e4, says Mayeux. But the study authors say that both ABCA7 and APOE-e4 are "major genetic risk factors" in blacks.

"This is a major finding because it shows that blacks have an additional risk factor compared to whites,'' says Neil Buckholtz, director of neuroscience at the National Institute on Aging, a branch of the National Institutes of Health. NIH 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."

APOE-e4 is associated with an increased number of amyloid plaques in the brain, which form into toxic clumps that destroy brain cells. Other processes, such as inflammation and insulin receptivity, are also being explored as possible contributors. ABCA7 also transports a precursor of amyloid plaques.

"We're definitely finding that there are layers to the disease,'' says Heather Snyder, a researcher for the Alzheimer's Association. She was not involved in this study. "We need to do more research to find out what these targets are doing in the brain so we can find treatments and ways of delaying the disease from starting."

About 5 million adults in the USA have Alzheimer's, and numbers are expected to more than triple by 2050 and cost $1.1 trillion a year annually. About a third of the people with late-onset Alzheimer's are 80 and older. It is the only disease among the top 10 killers that has no effective treatments.

Snyder says the Alzheimer's Association does not recommend people get genetic testing because the links aren't clearly established and some people who have the gene variants do not get the disease.

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