Objective: To develop a non-invasive diagnostic strategy for Parkinson’s disease (PD) via targeted 4D-metabolomics, identify PD-specific urinary amine-phenol biomarkers, and explore PD-related metabolic mechanisms.

Background: PD is a common neurodegenerative disorder, but non-invasive, specific early diagnostic biomarkers are lacking. Amine-phenol metabolites are associated with PD-perturbed neurotransmitter function and metabolism, and targeted 4D-metabolomics enables sensitive metabolite profiling for disease-specific signatures.

Method: A targeted 4D-metabolomics workflow (TIMS-Q-TOF-MS combined with dansyl chloride derivatization) was established to profile urinary amine-phenol submetabolome in 21 PD patients, 21 AD patients, and 21 healthy controls (HC). Partial least squares discriminant analysis (PLS-DA) verified analytical reliability; differential metabolites were screened by VIP > 1.2 and p < 0.05; ROC analysis evaluated diagnostic performance.A TIMS-Q-TOF-MS based 4D-metabolomics workflow (with dansyl chloride derivatization) profiled urinary amine-phenols in 21 PD, 21 AD patients and 21 HCs. PLS-DA, VIP>1.2/p<0.05, and ROC analysis were used.

Results: PLS-DA confirmed analytical reliability. Forty-seven PD-specific differential metabolites were identified, enriched in cysteine/methionine metabolism, phenylalanine-tyrosine-tryptophan biosynthesis, etc. Key perturbations included elevated dopamine 3-O-sulfate and reduced tryptophan. A three-metabolite panel achieved AUC 0.962 (95% CI: 0.912-1.00) for PD diagnosis, distinguishing PD from HC.

Conclusion: A sensitive, non-invasive targeted 4D-metabolomics workflow for urinary amine-phenol submetabolome was established. The identified PD-specific metabolites and three-metabolite panel provide a novel PD diagnostic strategy and insights into PD metabolic mechanisms, addressing the unmet need for early PD biomarkers.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/decoding-parkinsons-disease-metabolic-landscape-targeted-4d-metabolomics-of-urinary-amine-phenol-submetabolomes-for-specific-signature-identification-and-biomarker-discovery/