Gene Controls Age at Onset of Alzheimer’s and Parkinson’s Diseases
By applying a new technique that combines independent lines of genomic evidence, Duke University Medical Center researchers and colleagues have identified a single gene that influences the age at which individuals first show symptoms of Alzheimers and Parkinsons diseases.
Such genes that can impact patients age at onset for the two very prevalent neurological disorders are of particular interest as alternative targets for treatment, said Margaret Pericak-Vance, Ph.D., director of the Duke Center for Human Genetics. Drugs that delay the onset of Alzheimers or Parkinsons diseases beyond the normal human lifespan would effectively prevent them in patients at risk for the disorders, she added.
Alzheimers disease is the most common cause of dementia among people over the age of 65, affecting up to 4 million Americans. Parkinsons disease — characterized by tremors, stiffness of the limbs and trunk, slow movements and a lack of balance — afflicts approximately 50,000 Americans each year. Both are complex disorders involving multiple genes.
“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 Dukes Morris K. Udall Parkinsons 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 Alzheimers Association, the Institute de France, and the American Federation for Aging Research.
The teams earlier work identified a broad chromosomal region linked to the age at onset of Alzheimers and Parkinsons 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.
The researchers overlaid three independent lines of genetic evidence to reveal those genes more likely to play a role in the disorders age at onset — a method, called genomic convergence, which the Duke team developed.
The researchers first focused on Alzheimers disease by comparing the activity of genes in the hippocampus — a part of the brain affected by the disorder — of unaffected individuals and Alzheimers patients. The experiment uncovered four genes, including GSTO1, located in the region of the genome earlier linked to age at onset, the researchers report.
An additional analysis involving 1,773 patients with Alzheimers disease and 635 patients with Parkinsons 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 studys 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 Center for Human Genetics is one of five centers within Dukes Institute for Genome Sciences and Policy. The institute represents Duke Universitys comprehensive response to the broad challenges of the genomic revolution.
The international research team included scientists representing 17 institutions in the United States, the United Kingdom and Australia. Additional funding was provided by the Hilles Families Foundation, the U.S. Public Health Service, the California Department of Health Services, the Fran and Ray Stark Foundation Fund for Alzheimers Disease Research and GlaxoSmithKline.
contact sources :
Margaret Pericak-Vance Ph.D. , (919) 684-2063
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