Identification of metabolites reproducibly associated with Parkinson’s Disease via meta-analysis and computational modelling

Abstract

Abstract Many studies have reported metabolomic analysis of different bio-specimens from Parkinson’s disease patients. However, inconsistencies in reported metabolite concentration changes make it difficult to draw conclusions as to the role of metabolism in the occurrence or development of Parkinson’s disease. We reviewed the literature on metabolomic analysis of Parkinson’s disease patients. From 74 studies that passed quality control metrics, perturbations to 928 metabolites were reported to be associated with PD diagnosis, but only 190 were replicated with the same changing trends in more than one study. Of these metabolites, 60 exclusively increased, such as 3-methoxytyrosine and glycine, 54 exclusively decreased, such as pantothenic acid and caffeine, and 76 inconsistently changed in concentration in PD versus control subjects, such as ornithine and tyrosine. A novel genome-scale metabolic model of PD and corresponding metabolic map linking most of the replicated metabolites enabled a better understanding of the dysfunctional pathways of PD and prediction of additional potential metabolic markers from pathways with consistent metabolite changes to target in future studies.