Untargeted Plasma Metabolomics Unveils Distinct Metabolite Profiles in Parkinson Disease Subtypes: A Focus on idiopathic REM Sleep Behavior Disorders
Background: Parkinson’s disease (PD) is characterized by diverse clinical presentations and etiological complexities, with rapid eye movement (REM) sleep behavior disorder (RBD) serving as a prodromal marker. While extensive unbiased metabolic profiling of plasma samples from PD subjects has been conducted to identify novel PD metabolic biomarkers, comprehensive metabolic profiling of PD subtypes based on RBD status remains limited. Methods: We conducted a comprehensive metabolic profiling of PD subtypes at disease onset, considering the presence or absence of RBD, utilizing an untargeted metabolomics approach. Plasma samples were collected from subjects with PD with and without RBD at the initial stages of disease, idiopathic RBD, and healthy controls to elucidate similarities and differences among PD subtypes. Based on ordination analysis and metabolome-wide association study (Wilcoxon rank-sum tests and generalized fold changes), we identified specific groups of metabolites enriched