Is there a link between pesticide exposure and Parkinson’s disease (PD)? The question of association between environmental contaminants and neurological disorders is certainly not a novel one; and now, an epidemiological study published in the Feb. 4 print issue of Neurology adds to the growing body of evidence. UCLA researchers found that an individual's genetic makeup was a significant contributing factor in the strength of the pesticide and PD association; in the most exposed populations, individuals had a two- to six-fold increased risk of developing PD.
Led by Arthur G. Fitzmaurice, PhD, of the department of neurology at the David Geffen School of Medicine at University of California, Los Angeles, the authors of the paper had previously reported that a fungicide (benomyl) was associated with increased PD risk and damaged dopaminergic neurons by inhibiting in vitro and in vivo aldehyde dehydrogenase (ALDH) enzyme activity. For the Neurology paper, they set out to study whether environmental and genetic changes to neuronal ALDH enzymes increased risk of PD.
For the Neurology study, Dr. Fitzmaurice and colleagues developed an ex vivo assay to identify pesticides that could inhibit ALDH activity. These assays were then investigated for an association with PD within a population-based, case-control study called the Parkinson’s Environment & Genes Study. The study has been enrolling incident PD cases diagnosed no longer than 3 years before recruitment and population controls from 3 rural California counties (Fresno, Tulare, Kern) since 2001. The current study compared 360 patients with Parkinson's with 816 people from the same counties who did not have Parkinson's.
Of the 26 pesticides tested for their effects on neuronal ALDH activity, all of the metal-coordinating dithiocarbamates tested (e.g., maneb, ziram), two imidazoles (benomyl, triflumizole), two dicarboxymides (captan, folpet), and one organochlorine (dieldrin) inhibited ALDH activity, potentially via metabolic byproducts (e.g., carbon disulfide, thiophosgene), the authors reported. However, 15 screened pesticides did not inhibit ALDH.
Exposure to an ALDH-inhibiting pesticide was associated with two- to 6-fold increase in PD risk; genetic variation in ALDH2 exacerbated PD risk in subjects exposed to ALDH-inhibiting pesticides. Effect estimates for exposure at workplace addresses alone were smaller (odds ratio range: 1.25–2.58), and the 95% CI excluded the null only for maneb. When there was also a genetic variation in ALDH2, this exacerbated PD risk in subjects exposed to ALDH-inhibiting pesticides.
Dr. Fitzmaurice and co-authors concluded that ALDH inhibition plays a role in PD pathogenesis, and certain pesticides should be avoided to reduce the risk of developing PD. The findings also suggest “that therapies modulating ALDH enzyme activity or otherwise eliminating toxic aldehydes should be developed and tested to potentially reduce PD occurrence or slow or reverse its progression particularly for patients exposed to pesticides.”
See our previous coverage of the association between pesticide exposure and Parkinson’s risk: http://bit.ly/LLSqX4.