An important approach to an early diagnosis of Parkinsons disease (PD) is screening for peripheral biomarkers in patients at the early clinical stage. In this study, we evaluated catecholamine concentration changes in the tear fluid of untreated PD patients as biomarkers. Norepinephrine and dopamine concentrations in the tear fluid of patients were found to increase compared to those in age controls, which was especially pronounced on the side where motor symptoms appeared. On the contrary, the epinephrine concentration in the tear fluid of patients was reduced bilaterally. Since there was no reason to consider the markers found in the clinical stage of PD as markers of the preclinical stage, we additionally studied the tear fluid composition in mouse neurotoxic models of PD preclinical and clinical stages. The norepinephrine concentration in the tear fluid of mice from the clinical stage model was found to be higher than that in controls; in the preclinical stage model, the norepinephrine concentration had a tendency to increase. Therefore, both PD patients and mice from PD preclinical and clinical stage models manifest unidirectional changes in their tear fluid compositions, which may be considered as promising biomarkers for the development of early diagnosis.

This review provides information onthe non-motor peripheral manifestations of Parkinsons disease (PD) associated with a pathology of the visual analyzer and the auxiliary apparatus of the eye. The relationship between neurodegenerative processes that take place in the brain and in the eye opens new prospects to use preventive ophthalmologic examination todiagnose PD long before the characteristic motor symptoms appear. This will encourage the use of neuroprotective therapy, which stops, or at least slows down, neuronal death, instead of the current replacement therapy with dopamine agonists. Animportant result of an eye examination of patients with PD may be a non-invasive identification of new peripheral biomarkers manifesting themselvesas changes in the composition of the lacrimal fluid.

Development of differential and early (preclinical) diagnostics of Parkinson’s disease (PD) is among the priorities in neuroscience. We searched for changes in the level of catecholamines and α-2-macroglobulin activity in the tear fluid (TF) in PD patients at an early clinical stage. It was shown that TF in patients is characterized by an increased level of noradrenaline mainly on the ipsilateral side of pronounced motor symptoms (72%, p = 0.049), a decreased level of adrenaline on both sides (ipsilateral—53%, p = 0.004; contralateral—42%, p = 0.02), and an increased α-2-macroglobulin activity on both sides (ipsilateral—53%, p = 0.03; contralateral—56%, p = 0.037) compared to controls. These changes are considered as potential biomarkers for differential diagnosis. Similar changes in the TF were found in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice when modeling clinical and preclinical stages of PD. These data show the adequacy of models to the pathogenesis of PD along the selected metabolic pathways, and also suggest that the found TF changes can be considered as potential biomarkers for preclinical diagnosis of PD. In Parkinsonian mice, the level of catecholamines also changes in the lacrimal glands, which makes it possible to consider them as one of the sources of catecholamines in the TF.

Medical Academy Parkinson's disease (PD) is a multisystemic neurodegenerative disease involving different mediator systems, which has a wide spectrum of nervous and mental (emotional, cognitive, psychotic, and behavioral) disorders. Nervous and mental diseases are encountered in most patients with PD, at the same time they substantially lower quality of their life. The paper gives the present views of the pathogenesis and clinical presentation of nervous and mental disorders, and approaches to their therapy in PD.

No abstract

No 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 the 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. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control 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 the 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), were observed. The blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD.

М.Р. Нодель