Researchers have identified a genetic variation that may triple a person's chances of developing Alzheimer's disease. The finding, reported by two research groups in this month's Nature Genetics, could lead to a better understanding of the disease process and perhaps a new genetic test for the degenerative brain disease, which afflicts 20 million people worldwide.
One genetic link to Alzheimer's is already well established. People who inherit the gene for the e4 version of a brain protein called apolipoprotein E (apoE) have a more than fourfold-higher chance of developing a form of the disease relatively early. But the story is complicated: Many carriers never develop the disease, and many Alzheimer's patients do not carry the e4 version.
Looking for other genetic factors that may be at work, a team led by Fernando Valdivieso of the Universidad Autonoma de Madrid in Spain homed in on a DNA stretch near the gene for apoE on chromosome 19 that regulates the production of apoE. They found a variant of this regulatory region called 491A in 88 of 110 Alzheimer's patients tested, compared to 72 of 131 controls--translating to a threefold increase in disease risk for carriers. A second research group, led by Alison Goate of Washington University School of Medicine in St. Louis, found that 491A appeared to increase Alzheimer's risk by almost two times in a group of U.S. patients. The increased risk is independent of the e4 allele.
"The effect looks real," says Dennis Selkoe of Harvard University, although he cautions that the link needs to be confirmed in a much larger group of people. Goate and Valdivieso suspect that 491A might contribute to the formation of protein plaques, a hallmark of Alzheimer's disease, by stepping up production of apoE, the predominant protein in the plaques. If so, Goate says, it could be encouraging news for drug companies that are trying to develop ways to prevent plaque formation.