Parkinson’s Disease Is Predominantly an Environmental Disease

Abstract

Parkinson’s disease is the world’s fastest growing brain disorder, and exposure to environmental toxicants is the principal reason. In this paper, we consider alternative, but unsatisfactory, explanations for its rise, including improved diagnostic skills, aging populations, and genetic causes. We then detail three environmental toxicants that are likely among the main causes of Parkinson’s disease— certain pesticides, the solvent trichloroethylene, and air pollution. All three environmental toxicants are ubiquitous, many affect mitochondrial functioning, and all can access humans via various routes, including inhalation and ingestion. We reach the hopeful conclusion that most of Parkinson’s disease is thus preventable and that we can help to create a world where Parkinson’s disease is increasingly rare.

Parkinson’s Disease is Predominantly a Genetic Disease

“…This is also exemplified in the maps presented by Professors Dorsey and Bloem ( Fig. 2 in [ 138 ]), depicting geographic areas of overlap across the United States in PD incidence vis-à-vis use of/exposure to paraquat, TCE and other chlorinated solvents, and particulate matter.…”

“…One major issue relates to the increasing longevity of world populations with a concomitant increase in age-related disorders. On the surface, this phenomenon should similarly affect conditions like Alzheimer’s disease (AD) as much as it affects PD incidence and prevalence [ 138 ]. Still, there may be important differences between these age-related neurodegenerative disorders.…”

“…Conversely, it is currently difficult to envision a scenario where, for example, knowledge of a patient's remote history of neurotoxicant exposure could be directly "actionable". Nevertheless, experimental work prompted by findings from epidemiological studies has revealed many valuable mechanistic insights (e.g., MPTP and other neurotoxicants such as paraquat or TCE causing mitochondrial dysfunction [138,139] and more recently even pathological activation of LRRK2 kinase activity [140]). New avenues continue to be explored to understand the molecular mechanisms of PD based on epidemiological observations, for example with the study of caffeine [79,80,141] or nicotine [81,142] and related metabolites.…”

“…It has been argued that the rapid increase in PD cases worldwide, since its first formal description by James Parkinson slightly over 200 years ago ("from six to six million") [55], must be driven by environmental factors (given the relative stasis of innate biology over the same time frame), particularly industrialization and the widespread use of toxicants [55,138]. While there is little doubt that PD is common and poses an increasingly heavy burden on healthcare systems worldwide [3,6,157], the argument may be more multi-faceted than it appears at first glance.…”

“…In the absence of reliable in vivo diagnostic biomarkers [3,129], PD remains a clinical diagnosis, which can often be challenging [161][162][163]165]. Indeed, Professors Dorsey and Bloem highlighted that approximately half of PD cases detected during an extensive multicenter epidemiological survey conducted in China in the late 1990s had been undiagnosed prior to the study [138,166] (with rates of non-diagnosis as high as 90+% in rural communities [167]). It has been suggested that China's rapid increase in PD cases (more than doubling in age-adjusted PD prevalence between 1990 and 2016) is due to rapid industrialization [168,169], but it is likely that accompanying improvements in economic status and healthcare literacy, access to better healthcare (with improved diagnosis [161][162][163][164], as well as survival [164], of PD patients), and scientific interest in PD [6,170,171], have contributed substantially to the increased prevalence of PD.…”