The gene most often associated with Alzheimer’s disease doesn’t provide a complete picture of overall risk, according to researchers who analyzed family histories of the disease.

Previous research has shown that people with the E4 variant of the APOE gene have a greater risk of developing Alzheimer’s, but this new Duke University Medical Center-led study is one of only a few to examine the role of both APOE and family history together.

“We’ve learned that APOE genotype does not tell the whole genetic story. Other genes may be acting independently of APOE to influence someone’s risk for developing the disease,” lead investigator Kathleen A. Welsh-Bohmer, director of Duke’s Bryan Alzheimer’s Disease Research Center, said in a Duke news release.

The study included more than 5,000 people in Cache County, Utah, who were 65 and older when they were enrolled in the study in 1995. About 3,000 of the participants who provided DNA and details about their family history of Alzheimer’s were grouped according to the family history of the disease and whether they had the APOE E4 variant.

“Over an average of seven and a half years of observation, the people who experienced the most significant cognitive decline had a family history of the disease and one or more copies of APOE E4,” Kathleen M. Hayden, an assistant professor of geriatric psychiatry, said in the Duke news release.

“For this reason, researchers should focus not only on people at risk because of the APOE gene, but also those who have a family history of Alzheimer’s disease. Conversely, studying those who survive to late old age without disease is important to discover genes that may offer protection against the disease.”

The study was expected to be presented Tuesday at the Alzheimer’s Association’s International Conference on Alzheimer’s Disease, in Chicago.

“These data provide further evidence that we must explore other genetic avenues to learn more about who is at risk for cognitive decline and dementia,” Welsh-Bohmer said.

(Source: Duke University, news release, July 29, 2008)