Alzheimer's Clue

By Anastasia Toufexis

Only last year, Allen Roses, a Duke University neurologist, seemed out in left field in terms of research on Alzheimer's disease, the dread brain disorder that afflicts as many as 4 million Americans. His theory that a particular gene puts people at high risk for Alzheimer's just didn't get much attention or respect from fellow scientists. But after months of tirelessly making his case, Roses is no longer dismissed; instead he is being courted by drug companies eager to use his research to find a diagnostic test and treatment. At a medical meeting in New York City last week, Roses presented fresh evidence and stirred even more interest. No one, not even Roses, believes that he has answered all questions about Alzheimer's or that a cure is around the corner, but there is a growing consensus that the Duke scientist has opened up a promising avenue for understanding and attacking the disease.

For several years, researchers have known that the brain cells of Alzheimer's victims are clogged with an overabundance of beta amyloid. The sticky protein forms plaques that can kill the cells, gradually producing memory loss. But why do some people have an excess of the amyloid, and why does it accumulate in the brain?

Roses proposes that amyloid has an accomplice: a blood protein called ApoE. Its main function seems to be transporting cholesterol, but according to Roses, ApoE can also latch on to amyloid and cart it into brain cells. How often that happens may depend on what type of ApoE a person has, which in turn depends on the genes that direct the making of ApoE. Those genes come in at least three varieties -- dubbed E2, E3 and E4 -- and everyone has two of the genes, one from each parent.

Studies by Roses' team and others done on families hit by Alzheimer's suggest E4 raises the odds of getting the disease. For example, people with two E4 genes are eight to nine times as likely to have the disorder as those with two E3 genes. "Roses' genetic data are overwhelming," says Dr. Rudy Tanzi of Massachusetts General Hospital.

The theory doesn't explain every case: many people with E4 don't have Alzheimer's, and not all victims have E4. But the evidence indicating that E4 increases the risk may lead to a blood test to identify people likely to develop Alzheimer's. If Roses is right, the research may also help design a drug to keep ApoE from carrying so much amyloid into brain cells -- and thus prevent the proteins from doing their deadly work.

With reporting by Alice Park/New York