Two New Studies Show Complexity of Alzheimer's Disease Genetics

Alzheimer's Association
Wednesday, 22 July 1998

Two newly published research studies help clarify the role of genetics in Alzheimer's disease, yet also highlight the complex nature of the devastating, mind-robbing disorder that affects an estimated 4 million Americans, according to the Alzheimer's Association.

One study, by Rudolph Tanzi, Ph.D., director of the Genetics and Aging Unit at Massachusetts General Hospital, and colleagues, describes a new genetic variation associated with late-onset Alzheimer's, the most common form of the disease.

The second study, by Dr. John Breitner of the Department of Mental Hygiene at The Johns Hopkins University, suggests that the APOE gene, a generally accepted risk factor gene for Alzheimer's, may, in fact, influence only when a person gets Alzheimer's, but not whether they will get it. The two studies appear in the August 1998 issue of Nature Genetics.

"These are important new clues in the puzzle of Alzheimer's disease," said Zaven Khachaturian, Ph.D., director of the Association's Ronald & Nancy Reagan Research Institute. "As with all new scientific findings, but particularly with genetics, we need to see these results confirmed by other researchers using different subject groups."

Possible New Alzheimer's Disease Gene

"The greatest value in the findings by Dr. Tanzi and his group are the potential new insights about relationships between previously described findings on Alzheimer's disease," Khachaturian said. "The study suggests there may be a link between the known risk factor gene APOE, the process that creates the amyloid plaques in the brains of people with Alzheimer's and this new risk factor, alpha-2 macroglobulin. These linkages increase our understanding of this very complex disease, and show us that these factors are not occurring in isolation."

The new Alzheimer gene mutation on chromosome 12 discovered by Tanzi's group is thought to have added plausibility because the protein it codes for interacts with proteins coded for by two previously-identified Alzheimer genes — apolipoprotein E and amyloid precursor protein. However, the exact nature of these relationships is still unclear.

The researchers suggest the new mutation as a possible target for therapies, but they say it is not useful as a diagnostic tool.

Three genes have been identified for the rare, early-onset forms of Alzheimer's disease, which are estimated to affect between one and 10 percent of cases. A variant of the APOE gene is considered a risk factor for the more common, late-onset form of the disease. APOE comes in three forms or alleles, known as e2, e3 and e4. Every person has two alleles, one from each parent. Current thought is that persons having one or two e4 alleles are considered to be at higher risk for Alzheimer's.

For more information, or to contact Alzheimer's Association, see their website at: www.alz.org