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New Alzheimer's Risk Genes Identified
Date:5/11/2010

Finding could lead to future treatments, researchers say

TUESDAY, May 11 (HealthDay News) -- Scientists have pinpointed two genes that are linked to Alzheimer's disease and could become targets for new treatments for the neurodegenerative condition.

Genetic variants appear to play an important part in the development of Alzheimer's since having parents or siblings with the disease increases a person's risk. It is estimated that one of every five persons aged 65 will develop Alzheimer's disease in their lifetime, the researchers added.

Genome-wide association studies are increasing scientists' understanding of the biological pathways underlying Alzheimer's disease, which may lead to new therapies, said study author Dr. Sudha Seshadri, an associate professor of neurology at Boston University School of Medicine.

For now, people should realize that genes likely interact with other genes and with environmental factors, she added.

Maria Carrillo, senior director of medical and scientific relations at the Alzheimer's Association, said that "these are the types of studies we need in terms of future genetic analysis and things must be confirmed in much larger samples, as was done in this study."

The report is published in the May 12 issue of the Journal of the American Medical Association.

Although it was known that three genes are responsible for rare cases of Alzheimer's disease that run in families, researchers had been sure of only one gene, apolipoprotein E (APOE), that increased the risk of the common type of Alzheimer's disease, Seshadri noted.

Using a genome-wide association analysis study of 3,006 people with Alzheimer's and 14,642 people without the disease, Seshadri's group identified two other genes associated with Alzheimer's disease, located on chromosomes 2 and 19.

The first gene was close to a gene called BIN1 on chromosome 2 and the second was close to several genes, including EXOC3L2, BLOC1S3 and MARK4 on chromosome 19, the researchers noted.

Using another set of people with and without Alzheimer's, the researchers were able to confirm their findings.

Unfortunately, these genes added little to risk prediction for Alzheimer's disease since the effect of each of these individual genes is small, Seshadri said, so older people at risk for Alzheimer's should not rush out and ask for genetic testing for these new genes.

However, identifying each of these new genes points to new biological pathways involved in the development of Alzheimer's. Studying these pathways should lead to new ways to postpone, prevent and perhaps treat the disease, although such benefits are likely a decade away, Seshadri said.

Dr. Sam Gandy, associate director of the Alzheimer's Disease Research Center at Mount Sinai School of Medicine in New York City, said these findings need independent confirmation to increase the confidence that these are real Alzheimer's disease risk genes.

In addition, Gandy thinks where these genes are located could make them sensitive targets for new drugs.

Another expert, Greg M. Cole, associate director of the Alzheimer's Center at the University of California, Los Angeles, said that "this study confirms two previously identified genetic associations, but finds that they are not helpful as additional risk factors that add up and provide much better predictive power."

However, this study also finds two new significant links with other genes, he said. "If they are confirmed in further studies, this may tell us more about the neurodegeneration process and hopefully how to find drugs that stop it."

More information

For more on Alzheimer's disease, visit the Alzheimer's Association.



SOURCES: Sudha Seshadri, M.D., associate professor, neurology, Boston University School of Medicine; Sam Gandy, M.D., Ph.D., professor, neurology and psychiatry, and associate director, Alzheimer's Disease Research Center, Mount Sinai School of Medicine, New York City; Greg M. Cole, Ph.D., professor, medicine and neurology, and associate director, Alzheimer's Center, University of California, Los Angeles; Maria Carrillo, Ph.D., senior director, medical and scientific relations, Alzheimer's Association; May 12, 2010, Journal of the American Medical Association


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