Targeted metabolomics reveals altered carbohydrate and amino acid metabolism in Parkinson’s disease

Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder predominantly characterized by motor abnormalities. Its diagnosis remains challenging. Methods To explore potential blood-based metabolic signatures of PD, targeted metabolomic profiling of serum soluble metabolites was performed in three cohorts (levodopa-benserazide hydrochloride tablets [LBHT]-treated PD, LBHT-untreated PD, and normal controls [NC]). High-performance liquid chromatography (HPLC) was further used to measure selected metabolite levels for cross-method analytical confirmation. Results A total of 335 polar metabolites were identified. Among them, no differentially abundant metabolites were observed between the LBHT-treated and LBHT-untreated PD cohorts, whereas 5 and 16 metabolites showed nominal differences in the comparisons of LBHT-treated PD vs. NC and LBHT-untreated PD vs. NC, respectively. Glutamate, aspartate, γ-aminobutyric acid, and α-ketoglutarate were subjected to cross-method analytical confirmation by HPLC. Pathway enrichment analysis revealed alterations in carbohydrate and amino acid metabolism in PD patients, as reflected by decreased levels of glycolysis- and TCA-cycle-related metabolites and increased levels of aspartate-associated metabolites. ROC analysis suggested that reduced levels of 2-phosphoglycerate, 3-phosphoglycerate, cysteinylglycine, and succinate, together with elevated levels of aspartate, N-acetylaspartate, and N-acetylasparagine, showed preliminary potential as candidate biomarkers for distinguishing PD from controls. Conclusions This study suggests that PD is associated with alterations in carbohydrate and amino acid metabolism. These findings provide preliminary insights into the metabolic features associated with PD, although validation in larger, independent cohorts with comprehensive clinical phenotyping is warranted.