Health

UM researchers identify new gene associated with Alzheimer’s in African Americans

 

dchang@MiamiHerald.com

University of Miami medical school researchers working with geneticists and physicians from other institutions have identified a new gene associated with Alzheimer’s disease in African Americans, a finding that doctors say could help them prescribe more effective therapies and drugs for patients affected by the disease.

The collaborative study that led researchers from UM and other universities to identify the gene, called ABCA7, will be published Thursday in the Journal of the American Medical Association.

Dr. Margaret A. Pericak-Vance, director of UM’s John P. Hussman Institute for Human Genomics and one of the senior authors of the study, said the discovery of ABCA7 will allow researchers to develop therapies and drugs more specifically suited to African American patients affected by Alzheimer’s, a disease for which there is no prevention or cure.

While Alzheimer’s occurs as frequently in African Americans as other populations, Pericak-Vance said there are important differences in the molecular mechanisms of the disease among people of different races and ethnicities.

Identifying these differences, she said, may help researchers develop treatments and drugs that are more likely to be effective because they’re tailor-made for an individual’s genetic make-up.

For instance, the ABCA7 gene, which is found in people of all races, is a greater risk factor for Alzheimer’s among African Americans than it is among non-Hispanic whites, according to the study.

“There are going to be a lot of things that are similar across different races, different ethnicities,” she said. “But there’s also going to be some populations differences. When it comes to the point where we can translate these discoveries into therapies and prevention, we will need to understand all these nuances in order to find the right drug or the right therapy for that individual person.’’

Until this study, most clinical research into the genetics of Alzheimer’s involved patients of European descent, said Dr. Pascal Goldschmidt, dean of UM’s Miller School of Medicine.

The research project that led to the discovery of the new gene is believed to be the largest genome-wide association study conducted on late-onset Alzheimer’s disease in African Americans. It included 1,968 cases and 3,928 controls collected at multiple sites between 1989 and 2011.

Goldschmidt said 21st century medicine is heading in the direction of personalized healthcare, and doctors will need to understand the genetic differences among patients in order to maximize their care.

“We will be able to bring support to our patients that is what we call culturalized,’’ he said, “which means that it’s not only based on science but also based on what culture you come from, where is your ancestry from, what kind of gene pool you have been provided with.”

Pericak-Vance said that as researchers discover the effects of new risk factors specific to groups, such as the ABCA7 to African Americans, scientists also must learn how these genes work together in order to identify the most effective intervention for the disease.

“We need to see where the genetic landscape leads us as we put it together, as we paint the picture,’’ she said. “We have to take a system approach to see how they work together and where in the pathway of a gene you may want to intervene.’’

The ABCA7 gene is involved in the metabolism of fats, or lipids. It is associated with another gene called apolipoprotein E 4, or APOE4. Pericak-Vance was the first researcher to identify APOE4 as a risk variant in Alzheimer’s disease in 1993 while at Duke University.

The APOE4 gene accounts for more than 40 percent of all cases of Alzheimer’s, and remains the largest overall risk factor for the disease, according to UM researchers.

Because both the APOE4 and the ABCA7 genes are involved in lipid metabolism, researchers now know that the process is an important pathway of late-onset Alzheimer’s in African Americans, Goldschmidt said.

“It’s a huge deal,’’ he said of the gene discovery and its implications.

Currently, there are few treatments or drugs for Alzheimer’s, an irreversible brain disease that destroys memory and thinking. Some drugs may slow the disease’s progress, but they do not change the underlying process.

Pericak-Vance said the disease is “becoming an epidemic.’’

The National Institutes of Health estimates that Alzheimer’s affects an estimated 5 million people in the United States.

One of them is George Murray, 88, of Miami Gardens, who was diagnosed with Alzheimer’s in 2009, said his daughter, Shirley Gibson.

While the disease has taken a toll on Murray’s mind, Gibson, 69, said it can be harder on the caregivers. Gibson said her sister, Linda Mobley, 57, cares for Murray full-time.

“It’s a difficult disease to care for a loved one because, of course, they change,’’ she said. “You see a totally different person. And at some point, they don’t know you.’’

Gibson, the former mayor of Miami Gardens, said she gave a blood sample to UM researchers for the study that led to the discovery of the ABCA7 gene because she hopes the finding will lead to better medical care for African Americans.

“Seeing my father,’’ she said, “I wanted to participate, and I realized that not having our DNA in the studies is a major catalyst to not being able to get the kind of medicine, and to know what may be a cure for us or a treatment plan for African Americans, and how it should be different from some other group.’’

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