October 23, 2003
Activity Of Single Gene Influences Age Of Onset of Parkinson's, Alzheimer's

Duke University researchers discover that the activity level of a single gene influences the age of onset of both Parkinson's Disease and Alzheimer's Disease.

"Although physicians generally consider Alzheimer and Parkinson diseases to be distinct disorders, the two exhibit a lot of overlap both clinically and pathophysiologically," said Jeffery Vance, M.D., director of Duke's Morris K. Udall Parkinson's Disease Research Center and associate director of the Duke Center for Human Genetics. "This study emphasizes the similarity between the two diseases by highlighting a single gene that influences their age of onset."

The team reports their findings in the Dec. 15, 2003, issue (available online Oct. 21) of Human Molecular Genetics and will present the work as a keynote paper at the annual meeting of the American Society of Human Genetics, which will be held Nov. 4-8, in Los Angeles. The major funding for the study was provided by the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the Alzheimer's Association, the Institute de France, and the American Federation for Aging Research.

The team's earlier work identified a broad chromosomal region linked to the age at onset of Alzheimer's and Parkinson's diseases. The new research -- led by Pericak-Vance, Vance, John Gilbert, Ph.D. and Yi-Ju Li, Ph.D., of the Duke Center for Human Genetics and Jonathan Haines, Ph.D., of Vanderbilt University Medical Center -- narrows that region of the genome, which contained many hundreds of genes, to a single gene known as glutathione S-transferase omega-1 or GSTO1.

It is worth noting that glutathione serves as an intracellular antioxidant that gets oxidized in order to reduce free radicals to less harmful forms. It is not at all surprising that a gene playing a role in antioxidant metabolism would turn out to influence age of onset for two different neurodegenerative diseases. A body that expresses a higher level of genes that detoxify free radicals is, all else equal, not going to age as rapidly as one that expresses those genes at a lower level.

An additional analysis involving 1,773 patients with Alzheimer's disease and 635 patients with Parkinson's disease later found that of those four genes, only GSTO1 showed genetic differences associated with age at onset.

"By combining evidence based on gene expression and genetic association, we found a gene that modifies when the diseases start," said Li, the study's first author. "Understanding the role this gene plays in Alzheimer and Parkinson diseases may, in the future, lead to a means to delay the disorders' onset," she added, noting that even a short delay would benefit at-risk patients.

The development of drugs or gene therapies that would up-regulate genes for enzymes that are involved in quenching free radicals might work as an approach for slowing the general rate of aging and delaying the onset of degenerative disorders of the brain and of other parts of the body.

Share |      Randall Parker, 2003 October 23 02:21 PM  Aging Studies

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