Scientists at Oregon Health Sciences University, in collaboration with researchers at the University of California, Los Angeles, and four other Alzheimer's research centers have identified a gene that influences the age at which certain people begin to experience symptoms of Alzheimer's disease. Their findings appear in the Aug. 20, 1997 issue of Neurology and describe an association between a gene called HLA-A2 and the age of onset for Alzheimer's disease. This gene has long been known to play a role in the body's immune response.
"We are reporting the discovery of a new susceptibility gene for the common forms of Alzheimer's disease," said Haydeh Payami, Ph.D., lead author of the paper and associate professor of molecular and medical genetics and neurology at OHSU. Our study suggests that the age of onset for Alzheimer's disease is influenced by the HLA-A2 gene or a neighboring gene on chromosome 6 that is closely linked to HLA-A2. In the 207 Alzheimer's disease patients who were studied, those who had the HLA-A2 gene developed Alzheimer's disease at a younger age than those who did not carry the gene.
HLA-A2 is the second gene found to be associated with the common forms of Alzheimer's disease. The other susceptibility gene, apolipoprotein E (APOE), is also associated with the age of onset of Alzheimer's disease. Our study suggests that the two susceptibility genes HLA-A2 and APOE together account for a decade variation in the age of onset.
The study included two patient populations: one with 111 patients and the other with 96 patients. The second group was used as a confirmatory data set to validate the findings. Although the findings were validated, the authors emphasize the need for additional studies by other groups. The authors caution against generalized conclusions until the findings are replicated in other patient populations.
Alzheimer's disease is a devastating brain disorder that causes dementia and changes in personality. According to the Alzheimer's Association, the disease touches one in 10 families. It affects four million Americans who succumb to the disease and 19 million family members who care for them. Because Alzheimer's disease costs the U.S. economy $100 billion dollars annually, delaying the onset of symptoms by just one year will save the nation $10 billion.
"The next step is to pinpoint and isolate the culprit gene precisely as either HLA-A2 or another gene in the vicinity," says Payami. "Once the gene is in hand, we can figure out what it does and how it modulates the onset of Alzheimer's disease. By understanding the mechanism of action of these genes, we hope to devise intervention strategies to delay the onset of the disease."
The authors explain that Alzheimer's disease most likely involves the interaction of many genes and that if HLA-A2 plays a role, it is not an exclusive one.
Other collaborators from OHSU included Sepideh Zareparsi, Ph.D., Jeffrey Kaye, M.D., Gary Sexton, Ph.D., Mary Ann Head, Ph.D., and Douglas Norman, Ph.D. Participating researchers from UCLA and its affiliated medical center West Los Angeles Veterans Affairs Medical Center include senior author Gary Small, M.D., Steven Matsuyama, Ph.D., Lissy Jarvik, Ph.D., and Bruce Miller, Ph.D. Researchers from the University of Washington included Gerard Schellenberg, Ph.D., Thomas Bird, Ph.D., and Leonard Heston, Ph.D. Dennis McManus, Ph.D., from Southern Illinois University also contributed to the study as did Robert Katzman, Ph.D., from the University of California at San Diego.
The research was funded by grants from the National Institute on Aging at the National Institutes of Health, and the Alzheimer's Association.