Association of a five-metabolite and early-symptom profile with Parkinson’s disease and its clinical progression

Parkinson's disease (PD) urgently requires blood-based markers that flag pathology before disabling motor decline. This study measured absolute concentrations of 144 plasma metabolites in 20 neurologically healthy adults and in 40 PD patients clinically classified as intermediate (PD-I) or progressive (PD-II). A multinomial logistic regression model was built to examine how changes in metabolite concentrations relate to disease stage and to assess their exploratory discriminative performance in this cohort. Five metabolites: glutamine, butyric acid, indoleacetic acid, phosphatidylcholine aa C40:2, and acylcarnitine C12:1 emerged as the smallest biomarker set that consistently separated controls, PD-I, and PD-II. When three non-motor manifestations often present in the prodromal phase (drooling, REM behavior disorder and depression) were added, the combined profile clearly distinguished controls from early-stage patients and improved classification of intermediate versus progressive disease. The selected metabolites play roles in gut-derived signaling, mitochondrial β-oxidation, and membrane lipid homeostasis, while the clinical variables mirror the recognized early spread of α-synuclein pathology, together offering a coherent snapshot of systemic changes across PD progression. Because the panel can be quantified from a single small plasma aliquot and a brief clinical interview, it represents a promising exploratory finding that requires validation in larger, independent cohorts before any consideration for clinical application or pre-symptomatic screening.