Family History Has Complex Role in Alzheimer's Risk

Oct. 10, 2011 -- The role of family history on a person's risk for Alzheimer's disease appears to be more complex than previously recognized, a new study shows.

Scientists once thought that the bulk of genetic risk for late-onset Alzheimer's lay in a set of genes, called ApoE genes, that make a protein that carries cholesterol around the body.

Indeed, several companies have tried to capitalize on the connection between ApoE and Alzheimer's by offering tests that can tell people which version of the ApoE gene they carry.

Now a new study shows that people can still get the kind of brain changes linked to Alzheimer's if they have a family history but don't carry ApoE4, the gene thought to increase Alzheimer's risk.

The study is published in the Archives of Neurology.

"It's a really good study," says Robyn Honea, DPhil, an assistant professor in the Alzheimer's Disease Center at the University of Kansas School of Medicine in Kansas City, Kan. Honea was not involved in the research.

"This is showing that there are other mechanisms at work that are just as related to the disease process as ApoE4," Honea tells WebMD. "And the variety of biomarker tests that they're using in this study really makes that argument because they're really covering the gamut, looking for Alzheimer's-like brains in the most comprehensive way possible."

"This is going along with a lot of other data that myself and others are putting out there that there's a kind of unique genetic mechanism involved outside of this gene," Honea says.

Family History and Biomarkers for Alzheimer's

The study researchers recruited 269 healthy adults who were ages 45 to 75. The participants in the study lived in and around St. Louis.

Most of the volunteers (160) had at least one parent who had developed Alzheimer's before the age of 80. The rest didn't have a parent with Alzheimer's.

People in the study were given a variety of psychological and clinical tests. The psychological tests measured mental abilities like attention and memory. The clinical tests, which included spinal taps and brain scans, measured proteins that are known to accumulate in the brains of people with Alzheimer's disease as well as brain shrinkage. Blood tests were used to look for ApoE genes.

In people who had a family history of Alzheimer's, researchers found significant decreases in levels of beta-amyloid protein in spinal fluid. The lower level of beta-amyloid was true even if people didn't have an ApoE4 gene. There were no significant decreases in people who did not have a family history of the disease.

People in the study who had both a family history and who carried the ApoE4 gene had the largest drops in beta-amyloid in spinal fluid and had the biggest accumulations of beta-amyloid in their brains.

This suggests, experts say, that the presence of the ApoE4 gene is important, but that it doesn't tell the whole story.