Plasma acyl-carnitines, bilirubin, tyramine and tetrahydro-21-deoxycortisol in Parkinson's disease and essential tremor. A case control biomarker study

Abstract

Background and purpose: Given the overlapping clinical manifestations and pathology, the differentiation between essential tremor (ET) and Parkinson's disease (PD) is difficult. Our aims were to examine the plasma metabolomics profiling and their association with motor and non-motor symptoms (NMS) in patients with PD, and to determine differences between de novo PD compared to moderate-advanced PD vs. controls and patients with ET.

Methods: Plasma samples were collected from 137 subjects including 35 age matched controls, 29 NOVO-PD, 35 PD and 38 ET patients. PD severity, motor and NMS including cognitive function were assessed using the UPDRS, NMS and PD cognitive rating scales, respectively. Metabolomics analysis was performed by UPLC-ESI-QToF-MS followed by unsupervised multivariate statistics. The area under the curve of the biomarkers according to distribution of their concentrations and the diagnosis of PD (NOVO-PD, advanced PD) vs ET and healthy controls was used as a measurement of diagnostic ability.

Results: Several acyl-carnitines, bilirubin, tyramine and tetrahydro-21-deoxycortisol (THS) presented good predictive accuracy (AUC higher than 0.8) for differentiating de novo PD and advanced PD from controls and ET, suggesting an alteration in the lipid oxidation pathway. In multivariate regression analysis, metabolite levels were not significantly associated with motor and NMS severity in PD.

Conclusions: Diverse acyl-carnitines, bilirubin, tyramine and some adrenal gland derived metabolites are suggested as potential biomarkers able to distinguish between PD from controls and ET.

Keywords: Acyl-carnitines; Bilirubin; Essential tremor; Motor skills disorders; Parkinson's disease; Plasma biomarkers; Tetrahydro-21-deoxycortisol; Tyramine.