Pathogenic α‐synuclein triggers focal tau pathology, developing to various brain areas in Parkinson disease

Abstract

AbstractBackgroundParkinson disease (PD) is the second most common neurodegenerative disorder, whose prevalence is 2∼3% in the population over 65. Recent studies have reported enhancing confirmation of tau pathology in PD, however, α‐synuclein accumulation is the significant pathological hallmark of PD. Despite extensive considerations, thus far, the actual spreading mechanism of neurodegeneration has remained elusive in a PD brain. This study aimed to further clarification the development of α‐synuclein and tau pathologies.MethodWe employed several PD models, containing cultured neurons treated with either 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) or with recombinant α‐synuclein. Furthermore, we examined dopaminergic neurons of cytokine Interferon‐β knock‐out. Moreover, we tested rats administrated with 6‐hydroxydopamine, Rhesus monkeys injected with MPTP neurotoxin, and then human post‐mortem brains.ResultWe observed the α‐synuclein phosphorylation triggers tau pathogenicity. Moreover, we found more widespread phosphorylated tau than α‐synuclein with prion‐like nature in various brain areas. We optionally omitted P‐tau or P‐α‐synuclein from cytokine interferon‐β knock out with respective monoclonal antibodies. We observed that tau immunotherapy prevented neurodegeneration more than α‐synuclein exclusion.ConclusionOur observations show that the pathogenic tau could be one of the prominent causes of extensive neurodegeneration triggered by PD. Consequently, we could recommend an impressive therapeutic aims to fight the devastating disorder.