Circulating amino acid signature in older people with Parkinson's disease: A metabolic complement to the EXosomes in PArkiNson Disease (EXPAND) study

Background and aim: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in old age. Neurotoxicity of dopaminergic neurons triggered by aggregation of misfolded α-synuclein is a major pathogenic trait of PD. However, growing evidence indicates that peripheral processes, including metabolic changes, may precede and contribute to neurodegeneration. The present study was undertaken to identify a metabolic signature of PD through the quantification of serum amino acids and derivatives. Participants and methods: Twenty older adults with PD (11 men and 9 women; mean age 73.1 ± 10.2 years) and 30 age-matched controls (14 men and 16 women; mean age 74.6 ± 4.3 years) were enrolled. A panel of 37 serum amino acids and derivatives was assessed by ultra-performance liquid chromatography/mass spectrometry. Partial least squares − discriminant analysis (PLS-DA) followed by double cross-validation was used to characterize the relationship between amino acid profiles and PD. Results: The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classifications was 99.3 ± 2.5% for participants with PD and 94.7 ± 3.0% for non-PD controls. Higher levels of β-amino butyric acid, cystine, ornithine, phosphoethanolamine, and proline defined the circulating amino acid profile of older people with PD. Controls were characterized by higher concentrations of 3-methyl-histidine, citrulline, and serine. Conclusion: Our findings indicate the existence of a distinct metabotype in older persons with PD. Future studies will have to establish whether changes in amino acid metabolism are involved in the pathogenesis of PD. This knowledge may be harnessed to identify novel disease biomarkers as well as new targets for interventions.