New Gene Associated with Alzheimer's

Alzheimer's Association
Friday, 27 February 1998

The Alzheimer's Association is encouraged by newly published research that suggests there is another gene that may be associated with increased risk of Alzheimer's disease. It is especially interesting because it involved people with Alzheimer's who did not carry the known Alzheimer risk gene, APOE-e4, according to the Association.

"This is an intriguing, though preliminary, study," said Zaven Khachaturian, Ph.D., director of the Association's Ronald & Nancy Reagan Research Institute. "We need confirmation by other scientists with larger groups of patients before we can determine the true impact of this research.

"This finding provides further support to the growing body of evidence that there are multiple genes that affect a person's risk of getting Alzheimer's disease," Khachaturian said. "Also, it indicates a possible gene associated with increased risk for Alzheimer's in people who do not have the APOE-e4 gene."

APOE-e4 is currently the only generally accepted genetic risk factor for Alzheimer's disease. The study, by Robert Ferrell, Ph.D., and colleagues at the University of Pittsburgh Alzheimer's Disease Research Center, appears in the March 1998 issue of Nature Genetics. The team's clinical leader was Steven DeKosky, M.D., chair of the Association's Medical and Scientific Advisory Council.

The researchers studied 357 people with Alzheimer's disease and 320 normal controls. All were tested to find which types of a gene, known as the bleomycin hydrolase gene, they had. The gene has two forms, or alleles, known as A and G. People get two copies of the gene, one from each parent. The researchers found that people in their study who had two copies of the G allele, and did not have APOE-e4, were four times more likely to have Alzheimer's disease.

"It is evident there are many factors that contribute to the cause and progression of Alzheimer's, and almost certainly there are multiple genes involved. We need to track down these genes and find out how they interact with each other and with other risk factors in the environment," Khachaturian said. The Association is a strong supporter of increasing knowledge about what causes Alzheimer's, including the genetics of the disease, as a gateway to developing treatments.

Little is known about what the main function of bleomycin hydrolase is in the body. The only known function is to detoxify bleomycin, a widely used cancer drug. The researchers believe it may be involved in the process that generates amyloid plaques in the brains of people with Alzheimer's disease.

Knowledge of the genetics of Alzheimer's disease has been increasing since the early 1990s. Genetic information is important both in diagnosis and in discovering how the processes of Alzheimer's disease work.

The APOE gene encodes a protein that helps transport cholesterol around the body. In 1993, scientists noted that one variety of the gene, known as e4, appears to be associated with increased risk of sporadic Alzheimer's disease. APOE comes in three different forms, known as e2, e3 and e4. Genes for early-onset, familial Alzheimer's disease have been identified on chromosomes 1, 14 and 21. The study was funded in part by the National Institutes of Health and the Fiske Drug Discovery Fund.

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