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While LBs were first described a century ago, their formation and morphogenesis mechanisms remain incompletely understood. Here, we present a historical overview of LB definitions and highlight the importance of semantic clarity and precise definitions when describing brain inclusions. Recent breakthroughs in imaging revealed shared features within LB subsets and the enrichment of membrane-bound organelles in these structures, challenging the conventional LB formation model. We discuss the involvement of emerging concepts of liquid-liquid phase separation, where biomolecules demix from a solution to form dense condensates, as a potential LB formation mechanism. Finally, we emphasize the need for the operational definitions of LBs based on morphological characteristics and detection protocols, particularly in studies investigating LB formation mechanisms. A better understanding of LB organization and ultrastructure can contribute to the development of targeted therapeutic strategies for synucleinopathies.<\/jats:p>","DOI":"10.3233\/jpd-230183","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T10:47:20Z","timestamp":1704451640000},"page":"17-33","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Defining a Lewy Body: Running Up the Hill of Shifting Definitions and Evolving Concepts"],"prefix":"10.1177","volume":"14","author":[{"given":"Tim E.","family":"Moors","sequence":"first","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragomir","family":"Milovanovic","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, German Center for 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