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In LBD, not only the sole aggregation of \u03b1Syn but also the co-aggregation of amyloidogenic proteins, such as amyloid-\u03b2 (A\u03b2) and tau, has been reported. In this review, the pathophysiology of co-aggregation of \u03b1Syn, A\u03b2, and tau protein and the advancement in imaging and fluid biomarkers that can detect \u03b1Syn and co-occurring A\u03b2 and\/or tau pathologies are discussed. Additionally, the \u03b1Syn-targeted disease-modifying therapies in clinical trials are summarized.<\/jats:p>","DOI":"10.3390\/ijms241210215","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"10215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Mechanisms of the Roles of \u03b1-Synuclein, Amyloid-\u03b2, and Tau Protein in the Lewy Body Diseases: Pathogenesis, Early Detection, and Therapeutics"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2883-1773","authenticated-orcid":false,"given":"Moeko","family":"Noguchi-Shinohara","sequence":"first","affiliation":[{"name":"Department of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8454-6155","authenticated-orcid":false,"given":"Kenjiro","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The Parkinson Pandemic\u2014A Call to Action","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1002\/mds.22643","article-title":"The PRIAMO Study: A Multicenter Assessment of Nonmotor Symptoms and Their Impact on Quality of Life in Parkinson\u2019s Disease","volume":"24","author":"Barone","year":"2009","journal-title":"Mov. 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