Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and is imposing an increasing social and economic burden in ageing populations. Although the role of environmental factors has been recognised, few established risk factors have been consistently identified. Evidence that exposure to pesticides, herbicides and metals increase PD risk is suggestive, but further research is needed to identify specific compounds that may play a causal role.

Large established prospective population studies offer an important opportunity for investigating risk factors in relatively rare diseases such as PD. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 734 incident PD cases have been ascertained, for whom pre-diagnostic blood has been stored. A nested case-control study will be conducted, where one control per case will be selected by incidence density sampling matched by age at recruitment, sex and study centre.

Untargeted metabolomics can simultaneously characterize thousands of endogenous and exogenous compounds within a biological sample: the metabolome. Metabolome wide association studies (MWAS) have identified significant differences in the metabolomic profile of older adults with and without PD. We will employ an innovative approach combining liquid and gas phase chromatography with ultra-high-resolution mass spectrometry (LC/GC-UHRMS), to identify exogenous chemical exposures (e.g. pollutants, pesticides and medications), the exposome, in addition to the metabolome.

Disease specific variability in blood metabolite compositions may signify the presence of mechanistic aberrations contributing to PD pathogenesis. The combination of metabolome and exposome profiling provides a measure of the continuum from exposure to disease. Allowing previously unavailable richness and depth for characterizing the metabolome and exposome upon which novel discoveries in PD can be made.

The EPIC cohort allows us to perform a to study the metabolome and exposome well before disease onset, to eliminate possible effects of levodopa medication or disease-related processes.