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

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.

Keywords

• Parkinson’s disease
• biomarker
• metabolomics
• sphingomyelin
• phosphatidylethanolamine
• phosphatidylcholine