Alterations of Sphingolipid and Phospholipid Pathways and Ornithine Level in the Plasma as Biomarkers of Parkinson's Disease.

Kuo-Hsuan Chang,Mei-Ling Cheng,Chiung-Mei Chen,Hsiang-Yu Tang,Cheng-Yu Huang,Hsiu-Chuan Wu

doi:10.3390/cells11030395

Kuo-Hsuan Chang, Mei-Ling Cheng + Show 4 more

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https://doi.org/10.3390/cells11030395

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Abstract

The biomarkers of Parkinson’s disease (PD) remain to be investigated. This work aimed to identify blood biomarkers for PD using targeted metabolomics analysis. We quantified the plasma levels of 255 metabolites in 92 PD patients and 60 healthy controls (HC). PD patients were sub-grouped into early (Hoehn–Yahr stage ≤ 2, n = 72) and advanced (Hoehn–Yahr stage > 2, n = 20) stages. Fifty-nine phospholipids, 3 fatty acids, 3 amino acids, and 7 biogenic amines, demonstrated significant alterations in PD patients. Six of them, dihydro sphingomyelin (SM) 24:0, 22:0, 20:0, phosphatidylethanolamine-plasmalogen (PEp) 38:6, and phosphatidylcholine 38:5 and 36:6, demonstrated lowest levels in PD patients in the advanced stage, followed by those in the early stage and HC. By contrast, the level of ornithine was highest in PD patients at the advanced stage, followed by those at the early stage and HC. These biomarker candidates demonstrated significant correlations with scores of motor disability, cognitive dysfunction, depression, and quality of daily life. The support vector machine algorithm using α-synuclein, dihydro SM 24:0, and PEp 38:6 demonstrated good ability to separate PD from HC (AUC: 0.820). This metabolomic analysis demonstrates new plasma biomarker candidates for PD and supports their role in participating PD pathogenesis and monitoring disease progression.

Highlights

Introduction iationsParkinson’s disease (PD) is an age-related neurodegenerative disease characterized by bradykinesia, limb rigidity, postural instability, and freezing of gait
A total of 92 PD patients (71 patients at early stage and 21 patients at advanced stage) and 60 sex- and age-matched healthy controls (HC) were recruited in this study (Table 1)
The scores of Mini-Mental State Examination (MMSE), MoCA and Activities of Daily Living (ADL) were significantly lower in PD patients compared with HC (p = 0.005~

Summary

Introduction

Parkinson’s disease (PD) is an age-related neurodegenerative disease characterized by bradykinesia, limb rigidity, postural instability, and freezing of gait. The pathology is associated with progressive degeneration of dopaminergic neurons in the substantia nigra [1]. The pathogenesis of neurodegeneration in PD has not been fully disclosed. Several pathogenic pathways have been identified, including accumulation of aberrant or misfolded proteins, mitochondrial and metabolic dysfunction, increased oxidative stress and inflammation, and failure of mitophagy and autophagolysosome [1]. Effective treatments to prevent disease progression or modify the disease course for PD are not available. The main hurdle in developing an effective treatment for PD is the lack of objective and useful biomarkers to indicate early disease progression and to test the efficacy of potential treatments. The establishment of PD-specific molecular biomarkers, Licensee MDPI, Basel, Switzerland

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