{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:55:11Z","timestamp":1781564111967,"version":"3.54.5"},"posted":{"date-parts":[[2024,8,8]]},"group-title":"Neurology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To develop and externally validate models to predict probabilities of alpha-synuclein (a-syn) positive or negative status in vivo in a mixture of people with and without Parkinson\u2019s disease (PD) using easily accessible clinical predictors.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Uni- and multi-variable logistic regression models were developed in a cohort of participants from the Parkinson Progression Marker Initiative (PPMI) study to predict cerebrospinal fluid (CSF) a-syn status as measured by seeding amplification assay (SAA). Models were externally validated in a cohort of participants from the Systemic Synuclein Sampling Study (S4) that had also measured CSF a-syn status using SAA.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The PPMI model training\/testing cohort consisted of 1260 participants, of which 76% had manifest PD with a mean (\u00b1 standard deviation) disease duration of 1.2 (\u00b11.6) years. Overall, 68.7% of the overall PPMI cohort (and 88.0% with PD of those with manifest PD) had positive CSF a-syn SAA status results. Variables from the full multivariable model to predict CSF a-syn SAA status included age- and sex-specific University of Pennsylvania Smell Identification Test (UPSIT) percentile values, sex, self-reported presence of constipation problems, leucine-rich repeat kinase 2 (\n                    <jats:italic>LRRK2<\/jats:italic>\n                    ) genetic status and pathogenic variant, and\n                    <jats:italic>GBA<\/jats:italic>\n                    status. Internal performance of the model on PPMI data to predict CSF a-syn SAA status had an area under the receiver operating characteristic curve (AUROC) of 0.920, and sensitivity\/specificity of 0.881\/0.845. When this model was applied to the external S4 cohort, which included 71 participants (70.4% with manifest PD for a mean 5.1 (\u00b14.8) years), it performed well, achieving an AUROC of 0.976, and sensitivity\/specificity of 0.958\/0.870. Models using only UPSIT percentile performed similarly well upon internal and external testing.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Data-driven models using non-invasive clinical features can accurately predict CSF a-syn SAA positive and negative status in cohorts enriched for people living with PD. Scores from the UPSIT were highly significant in predicting a-syn SAA status.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.08.07.24311578","type":"posted-content","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T15:16:23Z","timestamp":1723130183000},"source":"Crossref","is-referenced-by-count":3,"title":["Predicting Cerebrospinal Fluid Alpha-Synuclein Seed Amplification Assay Status from Demographics and Clinical Data"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2394-9513","authenticated-orcid":false,"given":"Charles S.","family":"Venuto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3629-9337","authenticated-orcid":false,"given":"Konnor","family":"Herbst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-7196","authenticated-orcid":false,"given":"Lana M.","family":"Chahine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1645-6921","authenticated-orcid":false,"given":"Karl","family":"Kieburtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025032000300842000_2024.08.07.24311578v2.1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200878"},{"key":"2025032000300842000_2024.08.07.24311578v2.2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16041"},{"key":"2025032000300842000_2024.08.07.24311578v2.3","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-225111"},{"key":"2025032000300842000_2024.08.07.24311578v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00405-2"},{"key":"2025032000300842000_2024.08.07.24311578v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00404-0"},{"key":"2025032000300842000_2024.08.07.24311578v2.6","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.3311"},{"key":"2025032000300842000_2024.08.07.24311578v2.7","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28651"},{"key":"2025032000300842000_2024.08.07.24311578v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-021-00242-2"},{"key":"2025032000300842000_2024.08.07.24311578v2.9","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011935"},{"key":"2025032000300842000_2024.08.07.24311578v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-023-00519-8"},{"key":"2025032000300842000_2024.08.07.24311578v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2022.10.007"},{"key":"2025032000300842000_2024.08.07.24311578v2.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02358-9"},{"key":"2025032000300842000_2024.08.07.24311578v2.13","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29828"},{"key":"2025032000300842000_2024.08.07.24311578v2.14","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.0792"},{"key":"2025032000300842000_2024.08.07.24311578v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(23)00109-6"},{"key":"2025032000300842000_2024.08.07.24311578v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.09.005"},{"key":"2025032000300842000_2024.08.07.24311578v2.17","doi-asserted-by":"publisher","DOI":"10.2217\/bmm-2016-0366"},{"key":"2025032000300842000_2024.08.07.24311578v2.18","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-181434"},{"key":"2025032000300842000_2024.08.07.24311578v2.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00787-3"},{"key":"2025032000300842000_2024.08.07.24311578v2.20","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27646"},{"key":"2025032000300842000_2024.08.07.24311578v2.21","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51753"},{"key":"2025032000300842000_2024.08.07.24311578v2.22","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.162503"},{"key":"2025032000300842000_2024.08.07.24311578v2.23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2012.01974.x"},{"key":"2025032000300842000_2024.08.07.24311578v2.24","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207077"},{"key":"2025032000300842000_2024.08.07.24311578v2.25","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.774846"},{"key":"2025032000300842000_2024.08.07.24311578v2.26","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001265"},{"key":"2025032000300842000_2024.08.07.24311578v2.27","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-10229-3"},{"key":"2025032000300842000_2024.08.07.24311578v2.28","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51615"},{"key":"2025032000300842000_2024.08.07.24311578v2.29","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209656"},{"key":"2025032000300842000_2024.08.07.24311578v2.30","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab005"},{"key":"2025032000300842000_2024.08.07.24311578v2.31","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29340"},{"key":"2025032000300842000_2024.08.07.24311578v2.32","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.13075"},{"key":"2025032000300842000_2024.08.07.24311578v2.33","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09540-5"},{"key":"2025032000300842000_2024.08.07.24311578v2.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49402-x"},{"key":"2025032000300842000_2024.08.07.24311578v2.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-021-00259-7"},{"key":"2025032000300842000_2024.08.07.24311578v2.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106514"},{"key":"2025032000300842000_2024.08.07.24311578v2.37","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.772"},{"key":"2025032000300842000_2024.08.07.24311578v2.38","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01276-6"},{"key":"2025032000300842000_2024.08.07.24311578v2.39","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.635396"},{"key":"2025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