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At the same time, PD research is undergoing a profound conceptual transformation. Advances in molecular neuropathology, genetics, biomarker science, artificial intelligence, multimodal imaging, digital medicine, and precision therapeutics are reshaping PD from a clinically defined syndrome into a biologically measurable and potentially preventable process. This Perspective is not a report of new empirical findings and should not be read as an evidence-based forecast of what will most likely occur by 2050. Rather, it deliberately formulates a normative strategic vision: clinically manifest PD should become a preventable public-health burden. In this context, \u201ceradication\u201d does not imply elimination of all \u03b1-synuclein pathology, genetic susceptibility, or neurodegenerative biology. It refers to the long-term objective of preventing or substantially eliminating the transition to disabling, clinically manifest PD before irreversible symptomatic neurodegeneration occurs. We outline the prerequisites for such a future, including validated biological staging, risk stratification, longitudinal biomarker trajectories, trial enrichment, preventive endpoints, regulatory qualification, scalable implementation, and equitable global access. The analogy to poliomyelitis is used as a model of strategic goal-setting and international coordination, not as a biological equivalence between an infectious disease and a heterogeneous neurodegenerative disorder. Several enabling technologies already exist in early or research form, including \u03b1-synuclein seed amplification assays, genetic and prodromal risk models, digital monitoring, multimodal imaging, and mechanism-based therapeutic development. Other components remain aspirational and will require major scientific, regulatory, ethical, and societal advances. The central purpose of this article is therefore not to predict the future from the current trajectory, but to define a desired destination around which the field can organize scientific innovation.<\/jats:p>","DOI":"10.1007\/s00702-026-03240-x","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:25:20Z","timestamp":1785839120000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toward the prevention of clinically manifest Parkinson\u2019s disease"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-6187","authenticated-orcid":false,"given":"G\u00fcnter","family":"H\u00f6glinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Hopfner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"10423","key":"3240_CR1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0140-6736(23)01419-8","volume":"403","author":"Y Ben-Shlomo","year":"2024","unstructured":"Ben-Shlomo Y, Darweesh S, Llibre-Guerra J, Marras C, San Luciano M, Tanner CM (2024) The epidemiology of Parkinson\u2019s disease. 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