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The \u03b1Syn seed amplification methods in cerebrospinal fluid (CSF) showed high sensitivity and specificity for early diagnosis of PD and Lewy bodies disorders. Several studies in isolated REM sleep behavior disorders and other at-risk populations also demonstrated a high prevalence of CSF \u03b1Syn positivity and its potential value in predicting the phenoconversion to clinically manifested diseases. Growing evidence exists for \u03b1Syn aggregates in olfactory mucosa, skin, and other tissues in subjects with PD or at-risk subjects. DOPA decarboxylase and numerous other candidates have been additionally proposed for either diagnostic or prognostic purposes in earliest PD phases. The newly described \u03b1Syn detection in blood, through its quantification in neuronally-derived exosome vesicles, represents a technical challenge that could open a new scenario for the biological diagnosis of PD. Despite this growing evidence in the field, most of method of \u03b1Syn detection and markers still need to be validated in ongoing longitudinal studies through an accurate assessment of different prodromal disease subtypes and scenarios before being definitively implemented in clinical settings.<\/jats:p>","DOI":"10.3233\/jpd-240007","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T10:27:25Z","timestamp":1727432845000},"page":"S333-S344","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Biofluid Markers and Tissue Biopsies Analyses for the Prodromal and Earliest Phase of Parkinson\u2019s Disease"],"prefix":"10.1177","volume":"14","author":[{"given":"Andrea","family":"Pilotto","sequence":"first","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"},{"name":"Laboratory of Digital Neurology and 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