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Abstract

At Parkinson�s disease (PD) motor symptoms first appear many years after the onset of degeneration of nigrostriatal dopaminergic neurons that explains low efficiency of treatment. Therefore the development of preclinical diagnostics based on a search for biomarkers mainly as a change in the composition of plasma and expression of specific genes and phenotype of blood cells in drug-naive patients at the early clinical stage is of a high priority. Still, there is no guarantee that biomarkers, found at clinical stage are also a characteristic of preclinical stage. Therefore, we searched for biomarkers in experimental models of the earlier clinical and preclinical stages of PD (MPTP-treated mice) in addition to drug-naive patients shortly after the appearance of motor symptoms. According to our data, the concentration of some markers in plasma, e.g., L-DOPA, were modified in the same way in mice at the presymptomatic and symptomatic stages of Parkinsonism and patients. The concentration of others, e.g., DOPAC differed at the presymptomatic stage in mice from those in mice at the symptomatic stage and patients. Apparently, the former is more reliable than the latter. Moreover, we have developed at experimental models a novel complementary approach to the preclinical diagnosis of PD by using a pharmacological provocation test, which induces short-term increase of a failure of the nigrostriatal system and motor dysfunctions. Peripheral biomarkers and a positive provocation test, found at prophylactic examination of humans would allow including them in a risk group for the final diagnosis with positron emission tomography.

Biography

Email: mugrumov@mail.ru