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However, recent studies have demonstrated enhancing evidence of tau pathology in PD. Despite extensive considerations, thus far, the actual spreading mechanism of neurodegeneration has remained elusive in a PD brain. This study aimed to further investigate the development of \u03b1\u2010synuclein and tau pathology. We employed various PD models, including cultured neurons treated with either 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) or with recombinant \u03b1\u2010synuclein. Also, we studied dopaminergic neurons of cytokine Interferon\u2010\u03b2 knock\u2010out. Moreover, we examined rats treated with 6\u2010hydroxydopamine, Rhesus monkeys administrated with MPTP neurotoxin, and finally, human post\u2010mortem brains. We found the \u03b1\u2010synuclein phosphorylation triggers tau pathogenicity. Also, we observed more widespread phosphorylated tau than \u03b1\u2010synuclein with prion\u2010like nature in various brain areas. We optionally removed P\u2010tau or P\u2010\u03b1\u2010synuclein from cytokine interferon\u2010\u03b2 knock out with respective monoclonal antibodies. We found that tau immunotherapy suppressed neurodegeneration more than \u03b1\u2010synuclein elimination. Our findings indicate that the pathogenic tau could be one of the leading causes of comprehensive neurodegeneration triggered by PD. Thus, we can propose an efficient therapeutic target to fight the devastating disorder.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15257-fig-0012-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15257","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T22:44:20Z","timestamp":1606949060000},"page":"727-751","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["\u03b1\u2010synuclein abnormalities trigger focal tau pathology, spreading to various brain areas in Parkinson 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