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Modifying Risk Factors in Neurodegenerative Diseases

By Robin Arnette
September 2008

Ascherio
Ascherio, above, emphasized the potential of his findings about elevated urate levels. "This is the first molecular marker directly linked to both the risk of development and progression of PD." (Photo courtesy of Steve McCaw)

David Umbach, Ph.D.
Not surprisingly, the lecture attracted several of Chen's colleagues in the NIEHS Epidemiology and Biostatistics Branches, including biostatistician David Umbach, Ph.D., above. (Photo courtesy of Steve McCaw)

Fang Fang
Visiting Postdoctoral Fellow Sangmi Kim, Ph.D., turned to watch speakers during the question and answer session. Kim works with Principal Investigator and Epidemiology Branch Chief Dale Sandler, Ph.D. (Photo courtesy of Steve McCaw)

Rajendra Chhabra, Ph.D.
Ascherio's epidemiological studies also appealed to toxicologists, such as Rajendra Chhabra, Ph.D., center, group leader of the NIEHS General Toxicology Group. (Photo courtesy of Steve McCaw)

Parkinson's disease (PD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are debilitating neurodegenerative illnesses, but many researchers are making strides in understanding these conditions and developing treatment and prevention strategies. One of these investigators, Alberto Ascherio, M.D., Dr.P.H., a professor of Epidemiology and Nutrition at Harvard School of Public Health, presented a distinguished lecture at NIEHS titled "Environmental Risk Factors and Biomarkers of Neurodegenerative Diseases." Honglei Chen, M.D., Ph.D., a tenure track investigator in the Epidemiology Branch, hosted the seminar in Rodbell Auditorium on August 12.

Ascherio (http://www.hsph.harvard.edu/faculty/alberto-ascherio/)Exit NIEHS began his talk by identifying three major roles that the field of epidemiology contributes to public health: preventing disease, targeting individuals at high risk for disease and determining neuroprotective factors that could be used for people who have the disease. In the case of PD, Ascherio and others have investigated several factors associated with the disease, including smoking and the use of tobacco products, caffeine consumption, pesticide exposure and family history. His work with smoking and caffeine, however, has yielded surprising results.

"We used data from several longitudinal studies and continued them by sending follow-up questionnaires to participants," he said. "People who were current smokers or who had recently stopped smoking had a 70 percent lower chance of developing PD than those who had never smoked." He added, "Although smoking is a major cause of morbidity and mortality, that shouldn't blind us to the possibility that there is something among the hundreds of chemicals in cigarette smoke that is important in preventing PD."

Coffee, tea and soda also have hundreds of components, but a cohort that Ascherio led determined it was caffeine that protected against PD. Middle-aged men documented their caffeine consumption, and their health was monitored for the next 15 years. Decaffeinated coffee and non-coffee drinkers exhibited a higher risk of PD than those who regularly consumed caffeinated beverages.

Despite the findings with cigarette smoke and caffeine, Ascherio said that studies with the antioxidant urate were the most exciting. "[The elevated amount of] serum urate not only predicted a lower risk of PD, but also a slower progression of the disease," he said. To pursue the finding further, Ascherio and Michael Schwarzschild, M.D., Ph.D., from the MassGeneral Institute for Neurodegenerative Disease, are collaborating on a project to examine the safety and efficacy of elevating urate levels in patients with early PD. The work is being funded by the Michael J. Fox Foundation for Parkinson's Research.

In regard to MS, Ascherio said that Americans who lived in northern states had a higher risk of MS than those who lived in the South or Midwest; however, if a person from the North moved to the South, his or her risk decreased. One hypothesis suggested that the difference in MS risk was due to a reduction in vitamin D; people in higher latitudes receive less sunlight and are prone to vitamin D deficiency.

To test the idea, Ascherio measured 25-hydroxyvitamin D (25OHD) levels - a good marker for vitamin D - in blood samples from the Department of Defense Serum Repository and found an inverse relationship between 25OHD blood levels and risk of developing MS. Ascherio said, "If this is true, it suggests that MS is largely a preventable disease. If we could increase vitamin D levels within the U.S. population, we could reduce the risk of MS by one-half."

Ascherio ended the presentation with ALS research and highlighted a well-known study that found a relationship between veterans of the first Gulf War and ALS. He said that his group also found an increased incidence of ALS in military personnel who served during WWII, Korea and Vietnam. He said assembling over one million people for his next ALS cohort will be crucial. He noted, "Large longitudinal studies incorporating both genetic paths and biomarkers and environmental exposures are our best hope in finding or modifying risk factors in neurodegenerative diseases."



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