{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:34:52Z","timestamp":1790357692784,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuronal \u03b1\u2010synuclein disease (NSD) is defined by the presence of an in vivo biomarker of neuronal alpha\u2010synuclein (n\u2010asyn) pathology. The NSD integrated staging system (NSD\u2010ISS) for research describes progression across the disease continuum as stages 0 to 6.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim was to assess 5\u2010year longitudinal change in NSD\u2010ISS in early disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Analysis included a subset of participants from the Parkinson's Progression Markers Initiative (PPMI) enrolled before 2020 as Parkinson's disease (PD) patients, prodromal PD patients, or healthy controls (HC) who met NSD criteria. Staging was defined based on biomarkers of n\u2010asyn and dopaminergic dysfunction in early stages, clinical features, and severity of functional impairment in stages 3 to 6. Stages were determined annually for 5\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 576 NSD participants, 494 were enrolled as PD patients, 74 prodromal PD patients, and 8 HCs. At baseline, 24% of participants were stage 2B, 56% Stage 3, 13% stage 4, and less than 5% in other stages. At year 5, the respective percentages for stages 2B to 4 were 11%, 50%, and 34%, indicating progression through NSD stages. Progression was driven by functional impairment in the predominantly motor domain (95%) for stage 2B to 3, increasing degree of nonmotor dysfunction for stages 3 to 4 (46%), and a combination of domains for stages 4 to 5. Initiation of dopaminergic medications led to stage regression in 8% of participants in Stage 3 but 41% in stage 4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our analysis supports the utility of NSD\u2010ISS in defining the stages of disease progression, at least in the early clinical and prodromal stages (2B, 3, or 4), suggesting the value of NSD\u2010ISS as a potential research tool for drug development. Further research involving preclinical cohorts is a crucial next step. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.30191","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T03:35:14Z","timestamp":1745984114000},"page":"1318-1330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neuronal \u03b1\u2010Synuclein Disease Stage Progression over 5\u2009Years"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-1644","authenticated-orcid":false,"given":"Tanya","family":"Simuni","sequence":"first","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Gochanour","sequence":"additional","affiliation":[{"name":"Department of Biostatistics College of Public Health, University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuprita R.","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Biostatistics College of Public Health, University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-9989","authenticated-orcid":false,"given":"Michael C.","family":"Brumm","sequence":"additional","affiliation":[{"name":"Department of Biostatistics College of Public Health, University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Coffey","sequence":"additional","affiliation":[{"name":"Department of Biostatistics College of Public Health, University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3424-7143","authenticated-orcid":false,"given":"Kathleen L.","family":"Poston","sequence":"additional","affiliation":[{"name":"Department of Neurology Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana M.","family":"Chahine","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-7168","authenticated-orcid":false,"given":"Daniel","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pennsylvania and the Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Philadelphia Veterans Affairs Medical Center  Philadelphia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Tanner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Movement Disorders and Neuromodulation Center Weill Institute for Neuroscience, University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Gonzalez\u2010Latapi","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Kopil","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation for Parkinson's Research  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuge","family":"Xiao","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation for Parkinson's Research  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohini","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation for Parkinson's Research  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien","family":"Dam","sequence":"additional","affiliation":[{"name":"Neumora  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Pagano","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Critical Path for Parkinson's, Critical Path Institute  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Siderowf","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Dunn","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation for Parkinson's Research  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Marek","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Disorders  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the NSD Working Group the Parkinson's Progression Markers Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00405-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00404-0"},{"issue":"1","key":"e_1_2_10_4_1","article-title":"Neuronal alpha\u2010synuclein disease integrated staging system performance in PPMI, PASADENA, and SPARK baseline cohorts","volume":"10","author":"Dam TP","year":"2024","journal-title":"Nature Partners Journal"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.644"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2202867"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2203395"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207077"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22340"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","unstructured":"MarekK.The Parkinson's Progression Markers Initiative (PPMI) Clinical \u2010 Establishing a Deeply Phenotyped PD Cohort AM 3.2. protocols.io;2024.https:\/\/doi.org\/10.17504\/protocols.io.n92ldmw6ol5b\/v2.","DOI":"10.17504\/protocols.io.n92ldmw6ol5b\/v2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28715"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00109-6"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00787-3"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1184029"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29329"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29410"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23429"},{"key":"e_1_2_10_19_1","unstructured":"JobergD.ggsankey: Sankey Alluvial and Sankey Bump Plots. 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