A metabolic biomarker predicts Parkinson’s disease at the early stages in patients and animal models - Laboratoire de Neurosciences Expérimentales et Cliniques
Article Dans Une Revue The Journal of clinical investigation Année : 2022

A metabolic biomarker predicts Parkinson’s disease at the early stages in patients and animal models

David Mallet
Carole Carcenac
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Paola Bossù
Laure Verlin
  • Fonction : Auteur
Gianfranco Spalletta
Sabrina Boulet

Résumé

Background: Care management of Parkinson's disease (PD) patients currently remains symptomatic, mainly because diagnosis relying on the expression of the cardinal motor symptoms is made too late. Earlier detection of PD therefore represents a key step for developing therapies able to delay or slow down its progression.
Methods: We investigated metabolic markers in 3 different animal models of PD, mimicking different phases of the disease assessed by behavioral and histological evaluation, and in 3 cohorts of de novo PD patients and matched controls (n = 129). Serum and brain tissue samples were analyzed by nuclear magnetic resonance spectroscopy and data submitted to advanced multivariate statistics.
Results: Our translational strategy reveals common metabolic dysregulations in serum of the different animal models and PD patients. Some of them were mirrored in the tissue samples, possibly reflecting pathophysiological mechanisms associated with PD development. Interestingly, some metabolic dysregulations appeared before motor symptom emergence and could represent early biomarkers of PD. Finally, we built a composite biomarker with a combination of 6 metabolites. This biomarker discriminated animals mimicking PD from controls, even from the first, nonmotor signs and, very interestingly, also discriminated PD patients from healthy subjects.
Conclusion: From our translational study, which included 3 animal models and 3 de novo PD patient cohorts, we propose a promising biomarker exhibiting a high accuracy for de novo PD diagnosis that may possibly predict early PD development, before motor symptoms appear.

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Neurobiologie
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Dates et versions

hal-03577368 , version 1 (11-09-2024)

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David Mallet, Thibault Dufourd, Mélina Decourt, Carole Carcenac, Paola Bossù, et al.. A metabolic biomarker predicts Parkinson’s disease at the early stages in patients and animal models. The Journal of clinical investigation, 2022, 132 (4), pp.146400. ⟨10.1172/JCI146400⟩. ⟨hal-03577368⟩
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