ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurological Biomarkers
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1608031
This article is part of the Research TopicAdvancing personalized diagnosis and treatment in Parkinson's Disease: Integrating biomarkers, neuroimaging, and artificial intelligenceView all 11 articles
Metabolomic Profiling Uncovers Diagnostic Biomarkers and Dysregulated Pathways in Parkinson's Disease
Provisionally accepted
- Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
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Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, and it has an unclear pathogenesis and lacks validated and specificity biomarker-based diagnosis approaches, particularly in PD patients with rapid eye movement (REM) sleep behavior disorder (PD-RBD).Methods: Using untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics, serum profiles of 41 drug-naï ve PD patients (including 19 PD-RBD and 22 PD without RBD [PD-nRBD] patients) and 20 healthy controls (HCs) were analyzed.Results: Comparative analyses revealed 144 dysregulated metabolites in PD patients versus HCs, with 7 metabolites-sodium deoxycholate, S-adenosylmethionine, L-tyrosine,3-methyl-L-tyrosine, 4,5-dihydroorotic acid, (6Z)-octadecenoic acid, and allantoin-demonstrating high classification accuracy (area under the curve [AUC] > 0.93). Compared with PD-nPBD patients, PD-RBD patients exhibited distinct metabolic profiles, characterized by 21 differentially expressed metabolites, including suberic acid, 3-methyl-L-tyrosine, and methyl (indol-3-yl)acetate (AUC > 0.86). Notably, 3-methyl-L-tyrosine displayed dual dynamics, reflecting dopaminergic depletion in PD and compensatory metabolic adaptations in PD-RBD. Pathway enrichment analysis implicated central carbon metabolism (CCM) disruption in PD and peroxisome proliferator-activated receptor (PPAR) signaling pathway inactivation in PD-RBD. Conclusions: These findings reveal potential serum-based biomarkers for PD and PD-RBD, highlight CCM and PPAR pathways as therapeutic targets, and underscore the role of metabolic dysregulation in PD pathophysiology.
Keywords: Parkinson's disease, REM Sleep Behavior Disorder, Metabolomics, biomarkers, metabolic pathway
Received: 08 Apr 2025; Accepted: 19 May 2025.
Copyright: © 2025 Chen, Cheng, Pan, Yao, Lin, Fu and Pan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xinran Pan, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
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