Study Rationale: Although it is well known that exposure to environmental substances, including pesticides, contributes considerably to Parkinson’s disease (PD), the mechanisms are largely unexplored. Indeed, exposure alone may not be sufficient for the development of PD. Immune system disturbances, however, may generate vulnerabilities that facilitate PD pathogenesis after toxic exposures. Mounting evidence suggests that immune signals originating outside the brain are relevant to PD and that pesticides may induce immune alterations in addition to triggering neurotoxicity.
Hypothesis: We hypothesize that certain pesticides trigger PD and that pesticide exposure may act via systemic inflammatory events or immune system disturbances as well as neurotoxicity which facilitates PD pathogenesis.
Study Design: Using a population-based study, we will investigate whether and how immune system alterations relate to PD and disease progression. These immune profiles will include a combination of longitudinally measured cytokines, chemokines and serum growth factors, leukocyte counts, and immune-modulating microbiota measured in the fecal microbiome. We will also examine how specific pesticides and clusters of co-exposures are related to immune profiles. We have long-term, agricultural pesticide application records from a 30+-year period to assess exposure with residential and occupational proximity to applications in California’s Central Valley. We are targeting 68 pesticides and several co-exposure clusters which we have previously associated with PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: Immune dysfunction is likely a key element in PD. Obtaining a deeper understanding of how immune function is disrupted in people with PD and how environmental exposures contribute to these changes may provide novel mechanistic understandings of PD pathogenesis and suggest potential paths for early intervention and disease prevention.
Next Steps for Development: We foresee this research feeding into in-depth immunologic assessment, with functional assays, single-cell analyses and reactivity testing from individuals we identify as having been exposed to pesticides.