July 16, 2008
Researchers have identified a gene that may raise the risk of getting late-onset Alzheimer's, the most common form of the disease that typically strikes after age 65. Researchers hope that continued research into the gene and its effects on the brain and memory could one day lead to new drugs that help to modulate the course of Alzheimer's.
Dozens of genes are under investigation as possible contributing factors to Alzheimer's disease. Only one, called the APO-E4 gene, has been confirmed as a strong risk factor for late-onset disease, though not everyone who inherits this gene ends up with Alzheimer's. About 40 percent of those who develop late-onset Alzheimer's carry the APO-E4 gene.
The new gene, called CALHM1, does not appear to play nearly as an important role in Alzheimer's onset as the APO-E4 gene, experts say. However, it is more common, appearing in about a quarter of the population. The gene appears to increase the risk of getting Alzheimer's by about 45 percent, according to scientists at the Albert Einstein College of Medicine in New York. Having two copies of the gene may raise the risk by some 77 percent.
Several other genes have been linked to early-onset Alzheimer's disease, which can occur in a person's 40s or even younger but that accounts for only about 5 to 10 percent of Alzheimer's cases.
Calcium and the Brain
CALHM1 appears to interrupt the ability of brain cells to take in calcium. The mineral calcium is critical for nerve function, including brain cells critical for memory. The gene appears active in an area of the brain called the hippocampus, a seahorse-shaped area critical for memory and learning that is affected early in the course of Alzheimer's disease.
Different variants of the CLAHM1 gene also appear to influence levels of beta-amyloid, a protein that in its toxic form builds up in the brains of those with Alzheimer's. Beta-amyloid also makes up the plaques that form in the brains of those with the disease.
"We are very excited about the idea that CALHM1 could be an important target for anti-amyloid therapy in Alzheimer's disease," said researcher Philippe Marambaud of The Feinstein Institute for Medical Research and Albert Einstein College of Medicine.
The researchers hope that continued study of the gene and the role of calcium in memory loss may lead to better understanding of Alzheimer's. It may also allow for the development of new drugs that may be able to halt or reverse the memory and behavior problems of the disease.
The findings may help to explain some of the hereditary aspects of Alzheimer's disease. A study in March, for example, found that people whose parents both had Alzheimer's disease were more than twice as likely to develop the disease themselves. [See the article, "Risk of Alzheimer's Increases When Both Parents Have the Disease"]
But Alzheimer's is a complex disease that researchers are only now beginning to understand. In addition to genetic factors, lifestyle factors like diet and exercise, mental and social stimulation, advancing age, and other environmental components may all play a role in its onset.
It will likely take years of continued research to understand the roles of CALHM1 and other genes in memory and Alzheimer's. The new work appeared in the scientific journal Cell.
Dreses-Werringloer, U. Cell, June 27, 2008; Voume 133, pages 1149-1161.