Parkinson's Disease

Environmental Causes of PD

The vast majority of cases of PD are thought to be due to the interactions of genes and the environment. Environmental causes are presumed to be one or more ubiquitous but weak toxins, whose cumulative effects lead to disease in genetically predisposed individuals. The identity of these toxins is unknown, although several environmental risk factors have been identified through epidemiological studies.

A strong and consistent finding is that the risk of PD is increased by rural living, exposure to well water, and agricultural work, suggesting that pesticides and/or herbicides may cause or contribute to PD. These conclusions are strengthened by several identified toxins that induce parkinsonism in animal models, and even in humans.

The most striking such agent is MPTP, originally identified as a contaminant in a batch of "street heroin" in Berkeley, California in the 1980s. Addicts who injected it developed a clinical syndrome almost identical to PD. The identification of MPTP led to much productive work on the cellular pathogenesis of PD, including the recognition that inhibition of mitochondrial complex I can lead to substantia nigra cell death. However, numerous toxicological studies have demonstrated that MPTP itself is extremely rare in the environment, and thus is not a significant contributor to idiopathic PD.

Rotenone is a common garden insecticide that has been shown to cause parkinsonism in animal models, but it too has been ruled out as a major cause of PD. It remains to be seen if any single agent will eventually be shown to account for more than a small fraction of PD cases.

Genetic background is likely to affect the risk from pesticide exposure. A specific allele of one pesticide detoxification enzyme, glutathione transferase, was found to be less common among PD patients with a history of pesticide exposure. Among PD patients without such history, however, no difference in allelic distribution was found. This suggests that the allele exerted a protective effect for those exposed to pesticides.