A Pilot Study of Changes in the Level of Catecholamines and the Activity of α-2-Macroglobulin in the Tear Fluid of Patients with Parkinson’s Disease and Parkinsonian Mice

Abstract

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.

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage

“…Recently, we have proposed a third, hybrid approach to the development of the preclinical diagnosis of PD. It is based on a search for biomarkers in untreated PD patients at an early clinical stage, and in animal models of the preclinical and early clinical stages of PD [5,20,22]. In such case, only those changes in body fluids that are characteristic of both patients and animal models are considered as biomarkers of the preclinical stage.…”

Tear Biomarkers in Alzheimer’s and Parkinson’s Diseases, and Multiple Sclerosis: Implications for Diagnosis (Systematic Review)

“…Therefore, it seems justified to study the change in the profile of monoamine accumulation in tears as a potential source of PD biomarkers. Bogdanov et al (2021) [ 82 ] analyzed the change in the concentration of selected catecholamines (dopamine, noradrenaline, adrenaline), metabolites: L-DOPA (dopamine precursor) and DOPAC (dopamine degradation product). The study also analyzed the content of α-2-macroglobulin, which is a proteases inhibitor present in patients’ PD tears and involved in the pathogenesis of PD [ 82 ].…”

“…Bogdanov et al (2021) [ 82 ] analyzed the change in the concentration of selected catecholamines (dopamine, noradrenaline, adrenaline), metabolites: L-DOPA (dopamine precursor) and DOPAC (dopamine degradation product). The study also analyzed the content of α-2-macroglobulin, which is a proteases inhibitor present in patients’ PD tears and involved in the pathogenesis of PD [ 82 ]. The change in the regulation of this protein is observed in the CSF of people with PD [ 83 ].…”

“…Lactotransferin, clusterin, and beta-2-microglobulin were indicated in the group of immune response-related proteins with a high prognostic value. The authors note that these were a pilot study and that the analyses should be repeated in a larger population to validate them [ 82 ]. A valuable supplement to the knowledge about the PD substrate are the results of Acer et al (2022) [ 17 ], where authors are already jumping on protein candidates in the pre-clinical phase of PD.…”

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

“…This is due to the fact that MPTP is converted in the body into MPP+, a toxin of catecholaminergic neurons, which causes the death of these neurons in the brain, as well as in the peripheral nervous system in animals, which is also typical for patients [ 29 ]. Our MPTP models of PD at the preclinical and clinical stages were developed 10 years ago [ 28 ] and then used to assess the stage-dependent molecular mechanisms of neurodegeneration and neuroplasticity in the nigrostriatal dopaminergic system [ 25 , 30 , 31 ], as well as the peripheral manifestations of these processes [ 32 , 33 ].…”