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Association of a five-metabolite and early-symptom profile with Parkinson’s disease and its clinical progression
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  • Published: 21 January 2026

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

  • Juan José Oropeza Valdez1,2,
  • José Pedro Elizalde-Díaz3,
  • Osbaldo Resendis Antonio1,2,4,
  • Jaquelin Leyva -Hernández5,
  • Laura Adalid-Peralta5,
  • Mayela Rodríguez-Violante6,
  • Rupasri Mandal7,8,
  • David S. Wishart7,8,
  • Yamilé López-Hernández7,8,9 &
  • …
  • Eduardo Martínez -Martínez3 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biochemistry
  • Biomarkers
  • Diseases
  • Neurology
  • Neuroscience

Abstract

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 \(\beta\)-oxidation, and membrane lipid homeostasis, while the clinical variables mirror the recognized early spread of \(\alpha\)-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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

JJOV thanks the financial support from the UNAM Postdoctoral Program DGAPA.

Funding

This research was funded by Secretaría de Ciencia, Humanidades, Tecnología e Innovación ((64382 and CF-2023-I-1226)); INMEGEN internal funds (Basal 2025); Secretaría de Salud (FPIS2024-INMEGEN-6940); Genome Alberta (a division of Genome Canada) (grant number TMIC MC4); The Canadian Institutes of Health Research (CIHR) (grant number FS 148461); and The Canada Foundation for Innovation (CFI) (grant number MSIF 35456).

Author information

Authors and Affiliations

  1. Centro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México (UNAM), Mexico City, 04510, Mexico

    Juan José Oropeza Valdez & Osbaldo Resendis Antonio

  2. Human Systems Biology Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, 14610, Mexico

    Juan José Oropeza Valdez & Osbaldo Resendis Antonio

  3. Laboratory of Cell Communication and Extracellular Vesicles, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, 14610, Mexico

    José Pedro Elizalde-Díaz & Eduardo Martínez -Martínez

  4. Coordinación de la Investigación Científica – Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México (UNAM), Mexico City, 04510, Mexico

    Osbaldo Resendis Antonio

  5. Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, 14269, Mexico

    Jaquelin Leyva -Hernández & Laura Adalid-Peralta

  6. Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, 14269, Mexico

    Mayela Rodríguez-Violante

  7. The Metabolomics Innovation Centre, University of Alberta, Edmonton, AB T6G 1C9, Canada

    Rupasri Mandal, David S. Wishart & Yamilé López-Hernández

  8. Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada

    Rupasri Mandal, David S. Wishart & Yamilé López-Hernández

  9. SECIHTI-Metabolomics and Proteomics Laboratory, Academic Unit of Biological Sciences, Autonomous University of Zacatecas, Zacatecas, 98000, Mexico

    Yamilé López-Hernández

Authors
  1. Juan José Oropeza Valdez
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  2. José Pedro Elizalde-Díaz
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  3. Osbaldo Resendis Antonio
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  4. Jaquelin Leyva -Hernández
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  5. Laura Adalid-Peralta
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  6. Mayela Rodríguez-Violante
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  7. Rupasri Mandal
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  8. David S. Wishart
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  9. Yamilé López-Hernández
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  10. Eduardo Martínez -Martínez
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Contributions

Conceptualization was undertaken by José Pedro Elizalde-Díaz, Yamilé López-Hernández, Juan José Oropeza Valdez, and Eduardo Martínez Martínez; Methodology by Juan José Oropeza Valdez, Yamilé López-Hernández, Osbaldo Resendis Antonio, Rupasri Mandal, and José Pedro Elizalde-Díaz; Investigation by Juan José Oropeza Valdez, José Pedro Elizalde-Díaz, Jaquelin Leyva Hernández, Laura Adalid-Peralta, and Mayela Rodríguez-Violante; Data Curation by Juan José Oropeza Valdez and José Pedro Elizalde-Díaz; Formal Analysis by Juan José Oropeza Valdez, Osbaldo Resendis Antonio, and Rupasri Mandal; Software and Validation by Rupasri Mandal; Visualization by Juan José Oropeza Valdez and Osbaldo Resendis Antonio; Resources/Clinical Investigation by Mayela Rodríguez-Violante and Laura Adalid-Peralta; Writing – Original Draft by Juan José Oropeza Valdez and Yamilé López-Hernández; Writing – Review & Editing by all authors; Supervision by Yamilé López-Hernández, Eduardo Martínez Martínez, and David S. Wishart; Project Administration by Yamilé López-Hernández, David S. Wishart, and Eduardo Martínez Martínez; and Funding Acquisition by David S. Wishart, Yamilé López-Hernández, and Eduardo Martínez Martínez.

Corresponding authors

Correspondence to Yamilé López-Hernández or Eduardo Martínez -Martínez.

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Oropeza Valdez, J.J., Elizalde-Díaz, J.P., Antonio, O.R. et al. Association of a five-metabolite and early-symptom profile with Parkinson’s disease and its clinical progression. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36756-z

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  • Received: 01 July 2025

  • Accepted: 16 January 2026

  • Published: 21 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-36756-z

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Keywords

  • Metabolomics
  • Biomarker
  • Parkinson
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