Alzheimer’s risk almost double for African-Americans with gene variant

A gene variant dubbed ABCA7 nearly doubles chances of African Americans developing Alzheimer’s disease compared to African Americans without the variant. This particular gene variant plays a role in lipid and cholesterol homeostasis and lipid-targeting drugs may be sought to improve prevention and potentially treat this patient population, according research published in the April issue of the Journal of the American Medical Association.

An estimated 5 million Americans older than the age of 65 have been diagnosed with late-onset Alzheimer’s disease, an incurable neurodegenerative disease and the most common cause of dementia. This form of Alzheimer’s accounts for 90 percent of all patients. The gene ABCA7, also referred to as ATP-binding cassette sub-family A member 7, is only a minor variant for white patient populations, but for African Americans, it signals potential trouble.

Neurologist Christiane Reitz, MD, PhD, from Columbia University Medical Center in New York City, and colleagues joined the Alzheimer’s Disease Genetics Consortium to search for genetic variations that would explain why African Americans typically develop late-onset Alzheimer’s more than whites in the same community.

“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 Reitz. “Both genes raise the risk of Alzheimer’s in this population twofold.”

Genotyping disease-related variations helps researchers develop targets and biomarkers for genetic testing for disease risk and also plays a role in preventive measures and the development of potential therapies. African Americans are more likely to have cholesterol and lipid imbalances, thought to be a major culprit in cardiovascular disease, and researchers are beginning to look at these imbalances as a potential route for the development of Alzheimer’s disease. ABCA7 is also associated with amyloid, a ubiquitous protein that can form a plaque in the brain that is strongly associated with Alzheimer’s disease.

Previous studies looking at the genetic variant APOE-e4 showed definite connections between whites and development of the disease, but the role it plays with African Americans had been inconclusive until now. This study confirms that APOE-e4 affects African American risk as well as that of whites.

“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 Richard Mayeux, MD, MS, chair of neurology at Columbia University Medical Center.

A total of 5,896 African-American subjects, ages 60 years or older were recruited for the study from multiple sites between 1989 and 2011. Of these, 3,928 participants were diagnosed as cognitively normal and the remaining 1,968 were diagnosed with probable late-onset Alzheimer’s disease. The final set of single-nucleotide polymorphisms included 17,332,474 unique genetic variants.

Correlations between Alzheimer’s disease in genotyped single-nucleotide polymorphisms were evaluated in controlled data sets by case and based on family. Individual results were collected and an inverse variance–weighted meta-analysis was conducted for genomewide analyses and then for previous genetic reports. Results will have to be replicated for independent African-American study groups.

“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,” added Mayeux.