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First evidence recessive gene plays role in Alzheimer's disease
By Julie Buckles

An Arab community with unusually high rates of Alzheimer's disease provides the first evidence that a recessive gene may play a role in the degenerative condition, according to an expedited study in the current issue of Neurology.

Israeli and US researchers screened 821 elderly residents of Wadi Ara, a rural community in northern Israel. They found that 20 percent of residents over 65 had Alzheimer's, twice the usual rate, and that 60 percent of residents over 85 had the disease, compared to 40 percent in the general population.

Friedland anticipates identifying the specific recessive gene soon.

To date, only dominant genes have been linked with Alzheimer's disease. The epsilon 4 allele of the apolipoprotein E gene, or APOE-4, accounts for nearly all of the currently identified genetic risk associated with the most common form of Alzheimer's. Surprisingly, the residents of Wadi Ara exhibit the lowest levels of APOE-4 on record. Only four percent carry APOE-4, compared to 15 percent in the general population.

A recessive gene must be inherited from both parents to show its effect; a dominant gene needs only one parent. Because intermarriage among Israeli Arabs is the highest in the world—as high as 44 percent according to previous studies—researchers speculate that a recessive gene may account in part for the high frequency of Alzheimer's.

The Wadi Ara community is ideal for studying the role of recessive genes in Alzheimer's because of its large family sizes, high incidents of inbreeding and cooperative nature, says neurologist Robert Friedland, of the Alzheimer's Center at Case Western Reserve University in Cleveland, Ohio. Only 1.2 percent of the people refused to participate in the study, says Friedland, compared to refusal rates of 20 to 30 percent in the United States.

Researchers will next be looking to North America to determine whether the recessive gene is involved in causing Alzheimer's in other populations, says Friedland. A previous study indicates that Alzheimer's disease occurs at a higher rate in the Sanguenay region of Quebec, a Canadian community with high incidents of intermarriage.

Friedland anticipates identifying the specific recessive gene soon. "We're getting close," says Friedland, "but I can't disclose where in the genome we are."

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Bowirrat, A. et al. The very high prevalence of AD in an Arab population is not explained by APOE e4 allele frequency. Neurology 55, 731 (September 12, 2000).

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