Healthy middle-aged people who have a high-risk variant of a gene have less brain volume in areas affected early in Alzheimer’s disease and do worse on tests of memory and learning, researchers said. In one study released today, people with an average age of 54 and a version of a gene dubbed Tomm40 showed difficulty in learning and memory similar to those seen in early Alzheimer’s. Participants with the high-risk gene in a second study had less gray matter in parts of the brain involved in learning, memory, emotions and self-reflection.
The role of the Tomm40 variation, announced last year, was discovered by Duke University’s Allen Roses, who uncovered the variants in the APOE gene that predispose carriers to Alzheimer’s disease. Today’s findings suggest that Tomm40 may be useful for measuring risk of Alzheimer’s in middle age, said Sterling Johnson, a neuropsychologist at the University of Wisconsin School of Medicine and Public Health, who led the brain volume study, in a statement.
“These studies are beginning to show this genetic trait is correlating with physiological changes and structural changes before the disease,” said Roses, a co-author of the studies, in a telephone interview. “That’s the classic definition of a biomarker,” a feature that can be used to measure disease risk.
The results were presented at the International Conference on Alzheimer’s Disease in Honolulu.
$20 Test
A test to determine whether a person has Tomm40 won’t be commercially available until the clinical use has been established, said Roses, who is the director of the Deane Drug Discovery Institute at Durham, North Carolina-based Duke’s medical center. Such a test costs $20 for academic use, he said.
The researcher said he is in talks with four companies to commercialize an assay when the time comes, and declined to name the possible partners.
The long version of Tomm40 is the more-dangerous form, and signals an earlier onset of Alzheimer’s disease. It is usually found with a form of APOE known as APOE-4, the gene already shown to predispose carriers to Alzheimer’s disease, Roses’s earlier research found. Patients with another form, APOE-3, can get either a long version or a short version. Which one they get may help determine their Alzheimer’s susceptibility.
Mark Sager, a professor of preventive medicine at the University of Wisconsin medical school in Madison, led the study of middle-aged people with Alzheimer’s disease in their families. The patients had an average age of 57.
Regardless which version of APOE patients had, those with the higher-risk Tomm40 variant performed worse on tests of learning and memory, the research found. The participants had less gray matter in part of the brain called the cingulate cortex and the precuneus.
“In this study population, Tomm40 genotyping is allowing us to find evidence of very early Alzheimer’s disease at least 20 years before people begin to show the outward symptoms,” Sager said in a statement released by the Chicago-based Alzheimer’s Association, an advocacy group.
