Scientists in Israel and the U.S. report in today's issue of Neurology on the first evidence that may link a recessive gene--one that must be inherited from both parents--to some cases of Alzheimer's disease. Earlier work has implicated a number of dominant genes on three chromosomes--14, 19 and 21. And one of particular interest is the gene variant apolipoprotein E-4, or apoE-4, which is prevalent in people with late onset Alzheimer's. Among subjects in this new study, however, apoE4 was actually very rare.
These subjects were all elderly residents of Wadi Ara, a rural community in northern Israel. Amos Korczyn and his colleagues at Tel Aviv University, working with Robert Friedland of the Alzheimer's Center at Case Western Reserve University, screened 821 people in Wadi Ara and found that 60.5 percent of those over 85 had Alzheimer's, compared to about 40 percent elsewhere. But when they analyzed DNA samples taken at random from 256 study participants, they were surprised to discover that only 4 percent carried the apoE4 gene, compared to about 15 percent in other populations.
Although environmental factors may contribute to the high incidence of Alzheimer's in Wadi Ara (a possibility the researchers are investigating), they are more suspicious of an as yet unidentified recessive gene. Many marriages in the region are between relatives, a situation that greatly increases the risk of recessive traits appearing in a group. "We are hunting for this gene now," Korczyn says. "Identifying the gene would likely have a major impact on our understanding of how and why Alzheimer's occurs."