Abstract
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.
Highlights
Parkinson's disease (PD) is one of the most prevalent neurodegenerative disease in the world, affecting about 1% of adults older than 60 years(1)
In the early phases of Parkinson’s disease (PD), the “prodromal” phase is characterized by a panel of non-motor symptoms including neuropsychiatric disorders like apathy, which could schematically be defined as a loss of motivation(6), observed in up to 70% of PD patients(7)
PD diagnosis in humans relies on a scale which integrates evaluations of both neuropsychiatric and primarily motor symptoms(24), its final confirmation relies on postmortem histological evaluations which include dopaminergic loss in the nigro-striatal pathway leading to denervation of the DS, and the presence of alpha-synuclein containing Lewy Bodies
Summary
Parkinson's disease (PD) is one of the most prevalent neurodegenerative disease in the world, affecting about 1% of adults older than 60 years(1). In the early phases of PD, the “prodromal” phase is characterized by a panel of non-motor symptoms including neuropsychiatric disorders like apathy, which could schematically be defined as a loss of motivation(6), observed in up to 70% of PD patients(7). These symptoms are often premonitory of PD, they are not specific and cannot be considered as predictive criteria. Finding reliable, specific and highly predictive biomarkers of the prodromal stage of the disease is a substantial challenge for the success of PD curative or preventive strategies, and for the development of therapies able to delay or slow down PD progression(8, 9). Earlier detecting PD represents a key step for developing therapies able to delay or slow down its progression
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