A variation in the gene ABCA7 causes the risk of late-onset Alzheimer’s disease to double in African-Americans, according to a new study in JAMA.
The research, the largest analysis yet to establish genetic risk linked to late-onset Azheimer’s disease in African-Americans, was undertaken by the Alzheimer’s Disease Genetics Consortium and led by scientists from Columbia University Medical Center.
“Our findings strongly suggest that ABCA7 is a definitive genetic risk factor for Alzheimer’s disease among African-Americans,” said Richard Mayeux, MD, MS, professor and chair of Neurology at CUMC. “Until now, data on the genetics of Alzheimer’s in this patient population have been extremely limited.”
The ABCA7 gene plays a part in the production of lipids and cholesterol, which indicates that lipid metabolism might be a more crucial pathway for the disease in African-American individuals than in whites.
It is more common for African-Americans to experience lipid and cholesterol imbalances – which ultimately result in heart attacks, strokes, and vascular disease. Therefore, the authors explained that treatments that lower cholesterol and vascular disease could possibly be a successful way to decrease or delay Alzheimer’s among this group of people.
“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.
Almost 6,000 African-American volunteers over the age of 60 were involved in the research. About 2,000 of the subjects had Alzheimer’s and 4,000 were cognitively normal.
The experts aimed to look for genetic variants in African-Americans, who generally have an increased incidence of late-onset Alzheimer’s, compared to whites residing in the same community. Alzheimer’s affects approximately 5 million people aged 65 and older in the U.S., and 90% of all cases of the disease are reported to be the late-onset form.
Christiane Reitz, MD, PhD, first author and assistant professor of neurology, said:
“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. Both genes raise the risk of Alzheimer’s in this population twofold.”
The importance of the role of APOE-e4 in African-Americans had been unclear due to conflicting results from prior, smaller investigations.
“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 Dr. Mayeux, who is also co-director of the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain and the Gertrude H. Sergievsky Center at CUMC.
Many other genes that had recently been associated with the disease in white people were also shown in this report to have a role in African-Americans.
Dr. Reitz, who is a member of both the Sergievsky Center and the Taub Institute, explained:
“Because they cross ethnic groups, the likelihood increases that these genes are very important in the development of Alzheimer’s. And that gives us clues in our search for the cellular pathways associated with the disease. These findings suggest that the genetic underpinnings of Alzheimer’s disease may vary among different populations – and so should not be treated homogeneously.”
“These findings advance our understanding of genetic underpinnings that may play a role in disease onset and progression in African-Americans and suggest a novel target for therapeutic development,” Neil Buckholtz, PhD, of the National Institute on Aging, pointed out.
The ABCA7 gene also impacts the transport of many critical proteins, such as amyloid precursor protein, which is responsible for producing amyloid – the greatest source of the plaques that are found in the brains of patients with Alzheimer’s.
Therefore, there is more than one way that ABCA7 might play a part in an increased risk of late-onset Alzheimer’s disease among African-Americans.
In a recent study published in the journal Nueron, researchers were able to identify genes linked to the tau protein – a protein which develops in the brain of Alzheimer’s patients as the disease slowly progresses. Those genes include: GLIS3, TREM2, APOE, and TREML2.
The researchers said that their findings will help experts who are researching the cause of Alzheimer’s, as well as those trying to find ways of preventing it.
“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.
Although these findings may ultimately result in the development of genetic risk estimates specific to African-Americans, we are still a long way from being able to use genetic testing for Alzheimer’s, he added.
“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,” Dr. Mayeux explained.
Further research is necessary to replicate the results and prove that these genetic variants are significant predictors of Alzheimer’s.
Written by Sarah Glynn