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

David Mallet, Thibault Dufourd, Mélina Decourt, Carole Carcenac, Paola Bossù, Laure Verlin, Pierre-Olivier Fernagut, Marianne Benoit-Marand, Gianfranco Spalletta, Emmanuel L. Barbier, Sebastien Carnicella, Véronique Sgambato, Florence Fauvelle, Sabrina Boulet
Journal of Clinical Investigation. 2022-02-15; 132(4):
DOI: 10.1172/jci146400

Mallet D(1), Dufourd T(1), Decourt M(2), Carcenac C(1), Bossù P(3), Verlin L(4),
Fernagut PO(2), Benoit-Marand M(2), Spalletta G(5), Barbier EL(1)(4), Carnicella
S(1), Sgambato V(6), Fauvelle F(1)(4), Boulet S(1).

Author information:
(1)University Grenoble Alpes, INSERM, U1216, Grenoble Institut Neurosciences,
Grenoble, France.
(2)Université de Poitiers, INSERM U1084, Laboratoire de Neurosciences
Expérimentales et Cliniques, Poitiers, France.
(3)Dipartimento di Neurologia Clinica e Comportamentale, Laboratorio di
Neuropsicobiologia Sperimentale, IRCCS Santa Lucia Foundation, Rome, Italy.
(4)University Grenoble Alpes, INSERM, US17, CNRS, UMS 3552, CHU Grenoble Alpes,
IRMaGe, Grenoble, France.
(5)Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
(6)Université de Lyon, CNRS UMR5229, Institut des Sciences Cognitives Marc
Jeannerod, Bron, France.

BackgroundCare 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.MethodsWe 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.ResultsOur 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.ConclusionFrom 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.FundingFrench National Research Agency (ANR), DOPALCOMP, Institut
National de la Santé et de la Recherche Médicale, Université Grenoble Alpes,
Association France Parkinson.