Comprehensive Profiling of Blood Coagulation and Fibrinolysis Marker Reveals Elevated Plasmin-Antiplasmin Complexes in Parkinson's Disease.

Abstract

Simple SummaryA protein which was identified initially in nuclei and synapses of neurons and thus named alpha-synuclein (α-Syn) is significantly involved in Parkinson’s disease (PD). Mutations of the gene that codes for α-Syn cause familiar PD and α-Syn in sporadic PD has a tendency to form abnormal fibrils which are present in PD patients brains. α-Syn is also present in a variety of cells and biofluids, especially in red blood cells (erythrocytes), but also in plasma, saliva and platelets. This in turn raises the question whether presumably dysfunctional α-Syn affects the other enclosed constituents (haemoglobin, mediators of haemostasis, immunoglobulins and clotting factors). We thus searched for a potential impact in the aforementioned peripheral blood compartments in PD.Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. Accumulating evidence demonstrates that alpha-synuclein (α-Syn), an apparently predominant neuronal protein, is a major contributor to PD pathology. As α-Syn is also highly abundant in blood, particularly in red blood cells (RBCs) and platelets, this in turn raises the question on the function of presumably dysfunctional α-Syn in “peripheral” cells and its putative effect on the other enclosed constituents. Herein, we detected the internal variance in erythrocytes of PD patients by Raman spectroscopy, but no measurable amount of erythrocytic behavioural change (eryptosis) or any haemoglobin variation was noticed. An elevated level of plasmin-antiplasmin complexes (PAP) was observed in the plasma of PD patients, indicating activation of the fibrinolytic system, but platelet activation after thrombin stimulation was not altered. Sex-specific patterns were noticed for blood coagulation factor XIII and factor XII activity in PD patients. Additionally, the alterations in homocysteine levels which have often been observed in PD patients were found to be independent from L-DOPA usage and PAP levels. Furthermore, a selective gene expression analysis identified subsets of genes related to different blood-associated compartments (RBCs, platelets, coagulation-fibrinolysis) also involved in PD-related pathways.