A Genetic Clue To Alzheimer's Disease

victims by surprise. Researchers have spent years trying to figure out who's at risk for the devastating brain disorder, and why, but they've had no good answers. Now, thanks to Duke University neurologist Allen Roses, the picture is getting clearer. In two new studies, Roses and his colleagues show that the common form of Alzheimer's is often linked to a single errant gene. The discovery won't lead directly to new treatments, but it casts a bright light on the disease. "For 15 years we haven't had anything to go on," says neurologist Richard Mayeux of New York's Columbia Presbyterian Medical Center. "Now we do."

The new findings center on a blood protein called ApoE, which can take any of three forms (dubbed E2 through E4), depending on a person's genetic makeup. Everyone inherits two copies of the gene for ApoE, and the Duke findings suggest that people with at least one E4 variant are at the greatest risk. In one of the new studies, Roses's group analyzed tissue samples from more than 400 people and found that two thirds of Alzheimer's sufferers, but only one third of healthy controls, carried the E4 gene. In the second study, the researchers found that elderly people with one copy of the E4 gene suffered three times as much Alzheimer's as those with no E4. People with two copies of the gene were eight times as likely to be stricken.

Nearly a third of the population carries at least one copy of the E4 gene. Simple blood tests may soon enable people to check their status, but without better treatments, the knowledge won't do much good. The next challenge is to find out how the E4 protein might promote the disease. Researchers have already found the molecule amid the plaques and tangles of patients' brains, suggesting it plays a direct role in the disease process. A magic bullet for Alzheimer's may still be years away, but thanks to the new findings, researchers now have a target to shoot at.