Parkinson’s disease: a systemic inflammatory disease accompanied by bacterial inflammagens

Abstract

ABSTRACTParkinson’s disease (PD) is a well-known neurodegenerative disease. Recently, the role of gingipains fromPorphyromonas gingivaliswas implicated in Alzheimer’s disease. Here we present evidence of systemic inflammation, accompanied by hypercoagulation; we also show that ginipains fromP. gingivalisand its LPS may foster abnormal clotting, and that ginipains are present in PD blood, and thus that ginipain’s action on blood may be relevant to PD pathology. Bloods from both PD and healthy blood samples were analysed using thromboelastography (TEG), confocal and electron microscopies, and for cytokine and other circulating biomarkers. We also probed PD and healthy plasma clots with a polyclonal antibody for the bacterial protease, gingipain R1, fromP. gingivalis. Low concentrations of recombinant gingipain R1 were also added to purified fluorescent fibrinogen. TEG, fibrin(ogen) amyloid formation and platelet ultrastructure analysis confirmed profound hypercoagulation, while the biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. We provide evidence for the presence of the protease, gingipain R1 in PD blood, implicating inflammatory microbial cell wall products in PD.