New Genetic Clues to Alzheimer's Disease Unmasked Hunt Is on for 'Bad' Genes That Increase Risk

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By L.A. McKeown
WebMD Medical News

Reviewed by Dr. Jacqueline Brooks

A small group of elderly people from a rural area of northern Israel is helping scientists uncover some of the best-kept secrets of Alzheimer's disease.

Until now, researchers have been focusing on a specific gene that has been conclusively linked to an increased risk of developing the devastating disease, which has struck former President Ronald Reagan and millions of other aging people worldwide. The gene, known as apoE e4, is correlated with a higher risk of Alzheimer's disease in Americans, Europeans, and African-Americans. The more copies of apoE e4 a person has, the higher his or her risk is of getting the disease.

When they set out to study the elderly Arab population from the Israeli community of Wadi Ara, which has the highest rate of Alzheimer's in the world, the researchers began by sampling the residents' blood for apoE e4. Surprisingly, few people had it.

"It means that something else is a factor," says Amir Soas, MD, PhD, reporting on the study, which appears in the journal Neurology. Primary investigators Robert P. Friedland, MD, and Amos Korczyn, MD found that it is not necessarily apoE e4 in this population. Soas is director of Alzheimer project research at Case Western Reserve University Medical School in Cleveland.

In addition to having high rates of Alzheimer's and low rates of a major genetic risk factor, another thing that makes the people of Wadi Ara unusual is a high rate of intermarriage among relatives.

The new findings make sense, because if most cases of Alzheimer's are caused in part by multiple copies of "bad" genes, people with high rates of intermarriage, such as those in Wadi Ara, would naturally be at higher risk, says Creighton Phelps, PhD, director of the Alzheimer Disease Research Centers Program at the National Institute on Aging in Bethesda, Md. Phelps was not involved in the study.

Phelps says that if the research team, which includes scientists based in the U.S. and Israel, can identify a specific bad gene common to the Israeli group, it could further the understanding of patterns of Alzheimer's disease and help in the search for a treatment.

The gene, assuming the researchers can find it, probably produces a protein that contributes to deposits of plaque in the brain, which are characteristic of Alzheimer's disease. Pinpointing a specific gene and its protein would give researchers clues to finding ways to stop or inhibit the production of the protein, he says.

But the finding also makes things trickier for researchers, acknowledges Soas, because there may be many bad genes common to other tight-knit groups or communities that have yet to be discovered.

Another thing the researchers are interested in learning from the people of Wadi Ara is whether Alzheimer's disease strikes them at an earlier age. Most studies have looked at the incidence of Alzheimer's in people 65 and older, since disease incidence increases with increasing age. But the Israeli and American research team plans to go back to the Wadi Ara group and add people as young as 60 to the study to see if there is a higher incidence of disease in younger, as well as older, people. Soas says they also will look at a variety of other factors that could contribute to the higher risk of Alzheimer's.