metabolic profiling of Parkinson's disease and mild cognitive impairment

Abstract

Background: Early diagnosis of Parkinson's disease and mild cognitive impairment is important to enable prompt treatment and improve patient welfare, yet no standard diagnostic test is available. Metabolomics is a powerful tool used to elucidate disease mechanisms and identify potential biomarkers.

Objectives: The objective of this study was to use metabolic profiling to understand the pathoetiology of Parkinson's disease and to identify potential disease biomarkers.

Methods: This study compared the serological metabolomic profiles of early-stage Parkinson's patients (diagnosed < 12 months) to asymptomatic matched controls using an established array based detection system (DiscoveryHD4™, Metabolon, UK), correlating metabolite levels to clinical measurements of cognitive impairment.

Results: A total of 1434 serological metabolites were assessed in early-stage Parkinson's disease cases (n = 41) and asymptomatic matched controls (n = 40). Post-quality control, statistical analysis identified n = 20 metabolites, predominantly metabolites of the fatty acid oxidation pathway, associated with Parkinson's disease and mild cognitive impairment. Receiver operator curve assessment confirmed that the nine fatty acid oxidation metabolites had good predictive accuracy (area under curve = 0.857) for early-stage Parkinson's disease and mild cognitive impairment (area under curve = 0.759).

Conclusions: Our study indicates that fatty acid oxidation may be an important component in the pathophysiology of Parkinson's disease and may have potential as a diagnostic biomarker for disease onset and mild cognitive impairment. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's Disease; fatty acid beta oxidation; metabolomics.

Figure 1

a: Score plots of Principle Component 1 (PC1) versus Principle Component 2 (PC2) from principal component analysis (PCA) of post‐QC scaled metabolite data (n = 1393) in cases (red) and controls (black), showing corresponding centers of gravity (open squares). b: Comparative mean scaled intensities for the n = 20 significantly different metabolites between early‐stage PD (shaded) and age‐matched controls (unshaded), showing standard error of the mean. Highlighted are the nine metabolites associated with fatty acid beta oxidation. c: ROC curve of a logistic regression model for distinguishing early stage PD from matched controls using the 9 fatty acid beta oxidation (FAO) metabolites (where AUC is area under the curve). d: ROC curve of a logistic regression model for distinguishing MCI in early‐stage PD from cognitively normal early‐stage PD (Mild‐cognitive‐impairment‐normal MCI‐n); where AUC is area under the curve). [Color figure can be viewed at wileyonlinelibrary.com]