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The analysis of CSF\u2010\u03b1Syn\u2010SAA parameters may provide useful insight to dissect the heterogeneity of synucleinopathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess differences in CSF\u2010\u03b1Syn\u2010SAA amplification parameters in participants with PD stratified by rapid eye movement (REM) sleep behavior disorder (RBD), dysautonomia, <jats:italic>GBA<\/jats:italic>, and <jats:italic>LRRK2<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and CSF\u2010\u03b1Syn\u2010SAA data from the Parkinson's Progression Marker Initiative dataset were used. CSF\u2010\u03b1Syn\u2010SAA parameters included maximum fluorescence (F<jats:sub>max<\/jats:sub>), time to reach 50% of F<jats:sub>max<\/jats:sub> (T50), time to threshold (TTT), slope, and area under the curve (AUC). Sporadic PD (n\u2009=\u2009371) was stratified according to RBD and dysautonomia (DysA) symptoms. Genetic PD included carriers of pathogenic variants of <jats:italic>GBA<\/jats:italic> (<jats:italic>GBA<\/jats:italic>\u2010PD, n\u2009=\u200952) and <jats:italic>LRRK2<\/jats:italic> (<jats:italic>LRRK2<\/jats:italic>\u2010PD, n\u2009=\u2009124) gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CSF\u2010\u03b1Syn\u2010SAA was positive in 77% of <jats:italic>LRRK2<\/jats:italic>\u2010PD, 92.3% of <jats:italic>GBA<\/jats:italic>\u2010PD, and 93.8% of sporadic PD. The <jats:italic>LRRK2<\/jats:italic>\u2010PD cohort showed longer T50 and TTT, and smaller AUC than <jats:italic>GBA<\/jats:italic>\u2010PD (<jats:italic>P<\/jats:italic>\u2009=\u20090.029, <jats:italic>P<\/jats:italic>\u2009=\u20090.029, <jats:italic>P<\/jats:italic>\u2009=\u20090.016, respectively) and sporadic PD (<jats:italic>P<\/jats:italic>\u2009=\u20090.034, <jats:italic>P<\/jats:italic>\u2009=\u20090.033, <jats:italic>P<\/jats:italic>\u2009=\u20090.014, respectively). In the sporadic cohort, CSF\u2010\u03b1Syn\u2010SAA parameters were similar between PD with (n\u2009=\u2009157) and without (n\u2009=\u2009190) RBD, whereas participants with DysA (n\u2009=\u2009193) presented shorter T50 (<jats:italic>P<\/jats:italic>\u2009=\u20090.026) and larger AUC (<jats:italic>P<\/jats:italic>\u2009=\u20090.029) than those without (n\u2009=\u2009150).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CSF\u2010\u03b1Syn\u2010SAA parameters vary across genetic and non\u2010genetic PD subtypes at the group level. These differences are mostly driven by the presence of <jats:italic>LRRK2<\/jats:italic> variants and DysA. Significant overlaps in the amplification parameter values exist between groups and limit their use at the individual level. Further studies are necessary to understand the mechanisms of CSF\u2010\u03b1Syn\u2010SAA parameter differences. \u00a9 2024 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30085","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T07:36:06Z","timestamp":1734507366000},"page":"305-314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Association between the Amplification Parameters of the \u03b1\u2010Synuclein Seed Amplification Assay and Clinical and Genetic Subtypes of Parkinson's Disease"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-3914","authenticated-orcid":false,"given":"Piergiorgio","family":"Grillo","sequence":"first","affiliation":[{"name":"The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, Department of Neurology NYU Langone Health  New York City New York USA"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9454-8389","authenticated-orcid":false,"given":"Luis","family":"Concha\u2010Marambio","sequence":"additional","affiliation":[{"name":"Amprion, R&amp;D Unit  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8432-594X","authenticated-orcid":false,"given":"Antonio","family":"Pisani","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-5718","authenticated-orcid":false,"given":"Giulietta 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