Title : Development of the early diagnosis of parkinson’s disease at the prodromal stage
Abstract:
Parkinson’s disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains rather low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Advanced methodology used in this study included: (i) searching for patients at risk of developing prodromal PD based by premotor symptoms; (ii) searching for changes in the body fluids in these patients as diagnostic biomarkers; (iii) verifying the diagnosis of prodromal PD and diagnostic value biomarkers using positron emission tomography (PET); (iv) anticipating the development of motor symptoms. Out of 1835 patients, 26 patients were included in the risk group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found in plasma include a decrease in the concentrations of l-3,4-dihydroxyphenylalanine (L-DOPA) and urates, as well as the expressions of some types of microRNA, and an increase in the total oxidative status. In turn, in lymphocytes of patients at risk, an increase in the expression of the DA D3 receptor gene and the lymphocyte activation gene 3 (LAG3), as well as a decrease in the expression of the Protein deglycase DJ-1 gene (PARK7). These blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD. In subsequent PET study, the majority of patients at risk of developing PD showed a pronounced interhemispheric asymmetry in the incorporation of 18F-DOPA into dopamine synthesis in the striatum and some patients developed motor symptoms within a year. These data are considered as strong evidence for dopaminergic denervation of the striatum and the diagnostic value of identified blood biomarkers for prodromal PD.
