Vidyya Medical News Service
Volume 6 Issue 179 Published - 14:00 UTC 08:00 EST 27-Jun-2004 Next Update - 14:00 UTC 08:00 EST 28-Jun-2004
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Study sheds new light on genetic risk for Parkinson's disease

By combining the results of 22 studies, University of North Carolina at Chapel Hill researchers have found that a specific form of the gene APOE very slightly increases the risk of Parkinson's disease, even though the same gene is protective in Alzheimer's disease.

The researchers also found that the APOE-4 form of the gene, which has long been linked to an increased risk of Alzheimer's disease, is not a risk factor in Parkinson's disease.

A report of the findings appears this week in the June issue of the journal Neurology.

"It basically shows that neurodegenerative diseases may differ in significant risk factors, contrary to prevailing views," said lead author Dr. Xuemei Huang, assistant professor of neurology in UNC's School of Medicine.

The gene APOE refers to apoliprotein E, which takes three forms, or alleles: APOE-2, -3 and -4. These and other APO genes transcribe apolipoproteins, protein particles involved in lipid metabolism that shuttle these fatty acids, including cholesterol, through the body. "APOE-4 is a major susceptibility gene for sporadic and familial Alzheimer's disease and has been associated with poor clinical outcome in people with acute head injury and stroke," Huang said. "In the brain, apolipoprotein E-4 may be involved in neuron repair and in the removal of dead cells, so if you have APOE-4, you may be at higher risk of Alzheimer's disease or poor recovery from stroke and brain injury."

On the other hand, APOE-2 seems to occur with lower frequency in people with Alzheimer's disease and is linked with late onset of that disease's symptoms. The APOE type is linked to longevity and is more likely to be found in centenarians, she added. Thus, APOE-4 was perceived as the "bad guy" in neurological diseases, while APOE-2 was thought the "good guy."

"Although most people in the field believed this, the results of individual studies generally had not shown a significant link between APOE alleles and Parkinson's disease," she said.

These genotypes' influence on Parkinson's susceptibility is thought to be modest, as a number of factors may contribute. Thus, the number of subjects in an individual study may not have had enough statistical power to detect any links between gene type and Parkinson's, she added.

Huang and co-author Dr. Charles Poole, associate professor of epidemiology in UNC's School of Public Health, decided to enhance the statistical power through a technique called meta-analysis, combining 22 studies.

They included only studies that had both clear clinical or pathologic criteria for Parkinson's and the necessary APOE genotype information.

Combined, the selected studies had more than 2,000 patients and nearly 8,000 people without Parkinson's as a control group for comparison.

"We found that APOE-2 conveyed a slight but statistically significant risk for Parkinson's disease, with an odds ratio of 1.2," Huang said. "This means that people with this gene have about a 20 percent higher chance of developing Parkinson's disease than people without it. Given that the overall prevalence of Parkinson's in the general population is about 1 percent, this means the prevalence of the disease in people with APOE-2 is about 1.2 percent."

As to APOE-4, the putative "bad guy" in Alzheimer's disease risk, meta-analysis showed it had nothing to do with Parkinson's disease, said Huang.

The findings underscore the possibility of major differences in underlying disease processes among neurodegenerative disorders such as Alzheimer's and Parkinson's, which are often viewed as similar age-related disorders, the report said. The new results may be surprising, even paradoxical, Huang said, but she added that the Parkinson's field has been grappling with other paradoxes associated with the disease.

"Smoking and coffee consumption each are protective against Parkinson's symptoms. Both are associated with a decreased likelihood of developing Parkinson's disease. In susceptible people, no smoking, no coffee may increase the risk," Huang said.

"Our findings will not play a role in assisting a diagnosis of the disease; they are more aimed at understanding the disease. The findings may interplay with these paradoxes to help us unravel the complex origins of Parkinson's disease and perhaps find a way to prevent it."

The work was funded in part by a grant from the National Institute of Aging and National Institute of Environmental Health Sciences, components of the National Institutes of Health.

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