Potential Metabolomic Linkage in Blood between Parkinson's Disease and Traumatic Brain Injury.

Massimo Fiandaca,Thomas Johnson,Howard Federoff,Richard Wade-Martins,Mark Mapstone,Michele Hu,Kian Merchant-Borna,Thomas Gross,Amrita Cheema,Jeffrey Bazarian,Samuel Evetts

doi:10.3390/metabo8030050

Abstract

The etiologic basis for sporadic forms of neurodegenerative diseases has been elusive but likely represents the product of genetic predisposition and various environmental factors. Specific gene-environment interactions have become more salient owing, in part, to the elucidation of epigenetic mechanisms and their impact on health and disease. The linkage between traumatic brain injury (TBI) and Parkinson’s disease (PD) is one such association that currently lacks a mechanistic basis. Herein, we present preliminary blood-based metabolomic evidence in support of potential association between TBI and PD. Using untargeted and targeted high-performance liquid chromatography-mass spectrometry we identified metabolomic biomarker profiles in a cohort of symptomatic mild TBI (mTBI) subjects (n = 75) 3–12 months following injury (subacute) and TBI controls (n = 20), and a PD cohort with known PD (n = 20) or PD dementia (PDD) (n = 20) and PD controls (n = 20). Surprisingly, blood glutamic acid levels in both the subacute mTBI (increased) and PD/PDD (decreased) groups were notably altered from control levels. The observed changes in blood glutamic acid levels in mTBI and PD/PDD are discussed in relation to other metabolite profiling studies. Should our preliminary results be replicated in comparable metabolomic investigations of TBI and PD cohorts, they may contribute to an “excitotoxic” linkage between TBI and PD/PDD.

Highlights

Compelling epidemiological observations associate moderate and severe traumatic brain injury (TBI) and Parkinson’s disease (PD) [1]
We used receiver operating characteristic area under the curve (ROC AUC) results to compare classification of groups and specific biomarker panels in this investigation, with 1.0 indicating error-free classification and 0.5 indicating selection no better than by chance. Based on this preliminary investigation, there appears to be a reciprocal relationship in blood-derived Glutamic Acid levels between cases and controls in our subacute mild TBI (mTBI) and PD
Elevated blood-derived Glutamic Acid was noted in the TBI cases compared to controls, where the opposite was defined in the PD cohort

Summary

Introduction

Compelling epidemiological observations associate moderate and severe traumatic brain injury (TBI) and Parkinson’s disease (PD) [1]. Whether mild TBI (mTBI) is a significant risk factor for the development of PD (and other neurodegenerative disorders) has been more difficult to prove, due to fewer controlled investigations [2,3,4], conflicting results [5], and a lack of agreement on diagnostic criteria [6]. We anticipate that molecular phenotyping may resolve the latter discrepancies in the definition of mTBI. Absent a consensus regarding a potential post-traumatic etiology for PD (or dementing conditions), the future definition of such relationships likely requires comprehensive longitudinal investigations and novel biomarkers [9]. Despite the limitations in current knowledge, there is emerging agreement that chronic neuroinflammatory conditions are associated with clinical parkinsonism and/or dementia, if not true

Methods

Discussion

Conclusion