Metabolic profile in plasma and CSF of levodopa-induced dyskinesia in Parkinson’s disease: focus on neuroinflammation

Abstract

The existence of few biomarkers and the lack of a better understanding of the pathophysiology of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD) require new approaches, as the metabolomic analysis, for discoveries. We aimed to identify a metabolic profile associated with LID in patients with PD in an original cohort and to confirm the results in an external cohort (BioFIND). In the original cohort, plasma and CSF were collected from 20 healthy controls, 23 patients with PD without LID, and 24 patients with PD with LID. LC-MS/MS and metabolomics data analysis were used to perform untargeted metabolomics. Untargeted metabolomics data from the BioFIND cohort were analyzed. We identified a metabolic profile associated with LID in PD, composed of multiple metabolic pathways. In particular, the dysregulation of the glycosphingolipid metabolic pathway was more related to LID and was strongly associated with the severity of dyskinetic movements. Furthermore, bile acid biosynthesis metabolites simultaneously found in plasma and CSF have distinguished patients with LID from other participants. Data from the BioFIND cohort confirmed dysregulation in plasma metabolites from the bile acid biosynthesis pathway. There is a distinct metabolic profile associated with LID in PD, both in plasma and CSF, which may be associated with the dysregulation of lipid metabolism and neuroinflammation.