Human Genome Research Implicates Genes in Parkinson's
Nov. 13, 2001 -- It has long been suspected that genetic predisposition plays a role in a rare form of Parkinson's disease that occurs in young people. New research not only confirms that this is true, but for the first time identifies genes linked to the more common form of the devastating neurologic disorder that generally strikes late in life.
The findings provide strong evidence that Parkinson's disease has an important genetic component and is not caused by environmental factors alone, say researchers from Duke University Medical Center. They identified several genetic mutations that appear to be related to Parkinson's disease susceptibility, and say other, as yet unidentified, genes are probably involved. Their report appears in the Nov. 14 issue of the Journal of the American Medical Association.
This is the first step in trying to unravel what is a very complicated web of cause and effect," study leader William K. Scott, PhD, of Duke's Center for Human Genetics, tells WebMD. "For the first time, we have solid evidence that genetic factors are involved with the common form of Parkinson's. These factors probably interact with each other and the environment."
If future studies further clarify the role of genes in the development of Parkinson's disease, it is hoped this will lead to better treatments and better ways of identifying who is at risk for the disease. Approximately 1 million people in the United States have the neurodegenerative condition, which is characterized by tremors at rest, slowness, and a particular type of muscular rigidity. Actor Michael J. Fox, diagnosed at age 30, has the less common form of the disease, known as early-onset or young-onset Parkinson's.
Studies have long suggested that environmental factors such as pesticide exposure play an important causal role in Parkinson's. While this may be the case, the Duke findings challenge previous studies concluding that these factors are the primary cause of the disease.
Working with 16 institutions in the United States and Australia, the Duke team conducted complete genomic screenings of almost 900 people who either had Parkinson's or had two or more afflicted family members.
They confirmed earlier studies suggesting that mutations in the parkin gene play a role in early-onset Parkinson's disease. But the mutations were also found for the first time in people with late-onset disease. And a gene already linked to several rare neurological conditions and to Alzheimer's disease was also found to play a role in late-onset Parkinson's. Researchers found that variations in the tau gene appear to be directly involved in susceptibility to the disease.
"Tau by itself does not cause Parkinson's, but we found that a form of the tau protein may make some people susceptible to Parkinson's disease," says study author Jeffery M. Vance, PhD, MD. Vance is director of the Genomics Research Laboratories at the Duke genetics center.
The tau protein is important in maintaining the structure of brain cells. In Alzheimer's disease, malfunctioning tau causes proteins to bunch together in plaques and tangles easily identifiable at autopsy. But no such plaques or tangles are seen with Parkinson's, suggesting the protein may have a subtle role or that a closely-related gene might be the real culprit, Scott says.
"We don't see anything in the brains of people with Parkinson's that suggests tau is involved with causing the disease," he tells WebMD. "There is no obvious smoking gun, like there is in Alzheimer's. We can't even say for sure if we are seeing tau in Parkinson's or something genetically close to tau that has not yet been identified. We might be knocking on the next-door neighbor's door."