Early diagnosis of Parkinson’s disease: A cross-species biomarker

Background Care management of Parkinson’s disease (PD) patients currently remains symptomatic, especially because diagnosis relying on the expression of the cardinal motor symptoms is made too late. Detecting PD earlier therefore represents a key step for developing therapies able to delay or slow down its progression. Methods We investigated metabolic markers in three different animal models of PD, mimicking different phases of the disease assessed by behavioral and histological evaluation, and in 2 cohorts of de novo PD patients (n = 95). 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, non-motor signs and very interestingly, also discriminated PD patients from healthy subjects. Conclusion From our translational study which included three animal models and two PD patient cohorts, we propose a promising composite biomarker exhibiting a high level of predictivity for PD diagnosis in its early phase, before motor symptoms appearance. Fundings ANR, DOPALCOMP, Institut National de la Santé et de la Recherche Médicale, Grenoble Alpes University. ### Competing Interest Statement The authors have declared no competing interest. * 6-OHDA : 6-hydroxydopamine AUC : Area under the curve DS : Dorsal striatum GFP : Green fluorescent protein HRMAS : High resolution magic angle spinning MPTP : 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Nacc : Nucleus accumbens NMR : Nuclear magnetic resonance OPLS : Orthogonal partial least square OPLS-DA : Orthogonal partial least square discriminant analysis PD : Parkinson’s disease PDH : Pyruvate dehydrogenase PDHC : Pyruvate dehydrogenase complex PDP : Parkinson’s disease progression Pra : Pramipexole ROC : Receiver operating characteristic SNc : Substantia nigra pars compacta TH-IR : Tyrosine hydroxylase immunoreactivity Veh : Vehicle