Targeted serum metabolomics reveals alterations in amino acid and neurotransmitter pathways in Parkinson's disease

Abstract

Serum metabolomic profiling in Parkinson's disease (PD) remains underexplored. This study characterized alterations in serum amino acid and neurotransmitter levels in PD using targeted metabolomics and identified associated dysregulated metabolic pathways. A validated ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was employed to quantify 23 amino acids and 3 neurotransmitters in PD patients and controls. Logistic regression models assessed the relationship between motor phenotype and metabolomic profiles. An OPLS-DA model incorporating variable importance in projection scoring was applied to identify metabolic subtypes associated with disease progression. Significant differences were observed in the levels of 18 amino acids and 3 neurotransmitters between PD patients and controls (P < 0.001). Notably, glycine (Gly) and serine (Ser) levels were significantly reduced by 24% and 44% (P < 0.001), while proline level was elevated by 32% (P = 0.0004). Multivariate pathway analysis revealed three significantly perturbed metabolic pathways: arginine biosynthesis (P < 0.001), glyoxylate and dicarboxylate metabolism (P < 0.001), and Gly, Ser, and Thr metabolism (P = 0.013). These findings indicate that PD is associated with pronounced disruptions in serum amino acid and neurotransmitter metabolism. The cross-talk between these pathways offers new insights into PD pathogenesis.