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This review outlines the major developments and milestones in our understanding of PD that have shaped the way we define this disorder. Past criteria and definitions of PD have been based on clinical motor manifestations enabling diagnosis of the disease only in later symptomatic stages. Nevertheless, with advancing knowledge of disease pathophysiology and aim of early disease detection, a major shift of the diagnostic paradigm is being advocated towards a biological definition similar to other neurodegenerative disorders including Alzheimer\u2019s disease and Huntington\u2019s disease, with the ultimate goal of an earlier, disease course modifying therapy. We summarize the major pillars of this possible approach including in vivo detection of neuronal \u03b1-synuclein aggregation, neurodegeneration and genetics and outline their possible application in different contexts of use in the frame of biological PD definition.<\/jats:p>","DOI":"10.3233\/jpd-230411","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T12:04:11Z","timestamp":1710504251000},"page":"S257-S271","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":54,"title":["Defining Parkinson\u2019s Disease: Past and Future"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-1826","authenticated-orcid":false,"given":"Kristina","family":"Kulcsarova","sequence":"first","affiliation":[{"name":"Department of Neurology, P. J. Safarik University, Kosice, Slovak Republic"},{"name":"Department of Neurology, L. 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