First Evidence Of Recessive Gene In Alzheimer's Discovered

Researchers found that the high incidence of Alzheimer's was not caused, as might be expected, by a high incidence of the gene variant apolipoprotein E-4, or apoE-4, which is a major risk factor for the disease. In fact, apoE-4 showed up in this population at the lowest level on record, according to neurologist Amos Korczyn, MD, MSc, of Tel Aviv University in Israel.

Because marriages between people who are relatively closely related is common among Arabs who live in Israel, researchers speculate that a recessive gene may account in part for the high frequency of Alzheimer's. All of the genes identified as playing a role in Alzheimer's are dominant; no recessive genes have been linked to the disease. A dominant gene will show its effect if it is inherited from only one parent; a recessive gene must be inherited from both parents to show its effect.

"We are hunting for this gene now," Korczyn said. "Identifying the gene would likely have a major impact on our understanding of how and why Alzheimer's occurs. We would also then need to look at whether the gene is involved in causing Alzheimer's disease among other populations."

For the study, Israeli researchers and neurologist Robert Friedland, MD, of the Alzheimer's Center at Case Western Reserve University and the University Hospitals of Cleveland screened all of the elderly residents of Wadi Ara, a rural community in northern Israel. Of the 821 people, 60.5 percent of those over 85 years old had Alzheimer's disease, which is compared to a rate of about 40 percent found in other populations. In Wadi Ara, 20 percent of those over 65 had Alzheimer's, compared to the usual rate of about 10 percent found in other populations.

DNA samples were then taken at random from 256 of the study participants to determine whether they carried the apoE-4 gene. Four percent carried the gene; in other populations, approximately 15 percent of people carry the gene.

Other research has shown that 44 percent of all Arab marriages in Israel are consanguineous, or between people who are relatively closely related. "This population is ideal for studying the role of recessive genes in Alzheimer's and other diseases because of the large family size and the amount of intermarrying," said Friedland.

The researchers are also investigating whether environmental factors may play a role in the high rate of Alzheimer's in this population.

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The American Academy of Neurology, an association of more than 16,500 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research.

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