Upgraded Methodology for the Development of Early Diagnosis of Parkinson's Disease Based on Searching Blood Markers in Patients and Experimental Models.

Abstract

Numerous attempts to develop an early diagnosis of Parkinson's disease (PD) by searching biomarkers in biological fluids were unsuccessful. The drawback of this methodology is searching markers in patients at the clinical stage without guarantee that they are also characteristic of either preclinical stage or prodromal stage (preclinical-prodromal stage). We attempted to upgrade this methodology by selecting only markers that are found both in patients and in PD animal models. HPLC and RT-PCR were used to estimate the concentration of amino acids, catecholamines/metabolites in plasma and gene expression in lymphocytes in 36 untreated early-stage PD patients and 52 controls, and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice at modeling the clinical ("symptomatic") stage and preclinical-prodromal ("presymptomatic") stage of PD. It was shown that among 13 blood markers found in patients, 7 markers are characteristic of parkinsonian symptomatic mice and 3 markers of both symptomatic and presymptomatic mice. According to our suggestion, the detection of the same marker in patients and symptomatic animals indicates adequate reproduction of pathogenesis along the corresponding metabolic pathway, whereas the detection of the same marker in presymptomatic animals indicates its specificity for preclinical-prodromal stage. This means that the minority of markers found in patients-decreased concentration of L-3,4-dihydroxyphenylalanine (L-DOPA) and dihydroxyphenylacetic acid (DOPAC) and increased dopamine D3 receptor gene expression-are specific for preclinical-prodromal stage and are suitable for early diagnosis of PD. Thus, we upgraded a current methodology for development of early diagnosis of PD by searching blood markers not only in patients but also in parkinsonian animals.