{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:58:34Z","timestamp":1792547914884,"version":"4.5.0"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018231","name":"Aligning Science Across Parkinson&apos;s","doi-asserted-by":"publisher","award":["ASAP-237603"],"award-info":[{"award-number":["ASAP-237603"]}],"id":[{"id":"10.13039\/100018231","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson&apos;s Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.ebiom.2025.105866","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T16:03:20Z","timestamp":1754496200000},"page":"105866","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Baseline \u03b1-synuclein seeding activity and disease progression in sporadic and genetic Parkinson's disease in the PPMI cohort"],"prefix":"10.1016","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4227-4710","authenticated-orcid":false,"given":"Jackson G.","family":"Schumacher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Macklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Bayati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7097-3826","authenticated-orcid":false,"given":"Johannes M.","family":"Dijkstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8553-8536","authenticated-orcid":false,"given":"Hirohisa","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Schwarzschild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Cortese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiqun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ebiom.2025.105866_bib1","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2018.00612","article-title":"Parkinson's disease: biomarkers, treatment, and risk factors","volume":"12","author":"Emamzadeh","year":"2018","journal-title":"Front Neurosci"},{"key":"10.1016\/j.ebiom.2025.105866_bib2","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.ebiom.2025.105866_bib3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13024-020-00368-6","article-title":"Initiation and propagation of \u03b1-synuclein aggregation in the nervous system","volume":"15","author":"Hijaz","year":"2020","journal-title":"Mol Neurodegener"},{"key":"10.1016\/j.ebiom.2025.105866_bib4","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00702-002-0808-2","article-title":"Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen","volume":"110","author":"Braak","year":"2003","journal-title":"J Neural Transm (Vienna)"},{"key":"10.1016\/j.ebiom.2025.105866_bib5","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00401-009-0538-8","article-title":"Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction","volume":"117","author":"Beach","year":"2009","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.ebiom.2025.105866_bib6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson's disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol Aging"},{"key":"10.1016\/j.ebiom.2025.105866_bib7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s40478-021-01282-8","article-title":"High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson's disease","volume":"9","author":"Russo","year":"2021","journal-title":"Acta Neuropathol Commun"},{"key":"10.1016\/j.ebiom.2025.105866_bib8","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000210279","article-title":"\u03b1-Synuclein seed amplification assay amplification parameters and the risk of progression in prodromal Parkinson disease","volume":"104","author":"Coughlin","year":"2025","journal-title":"Neurology"},{"key":"10.1016\/j.ebiom.2025.105866_bib9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s40478-021-01276-6","article-title":"Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson's disease and dementia with Lewy bodies","volume":"9","author":"Brockmann","year":"2021","journal-title":"Acta Neuropathol Commun"},{"key":"10.1016\/j.ebiom.2025.105866_bib10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41531-023-00627-5","article-title":"CSF \u03b1-synuclein seed amplification kinetic profiles are associated with cognitive decline in Parkinson's disease","volume":"10","author":"Brockmann","year":"2024","journal-title":"NPJ Parkinsons Dis"},{"key":"10.1016\/j.ebiom.2025.105866_bib11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41531-024-00854-4","article-title":"Radiological markers of CSF \u03b1-synuclein aggregation in Parkinson's disease patients","volume":"11","author":"Droby","year":"2025","journal-title":"NPJ Parkinsons Dis"},{"key":"10.1016\/j.ebiom.2025.105866_bib12","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1002\/alz.13658","article-title":"Investigating alpha-synuclein co-pathology in Alzheimer's disease by means of cerebrospinal fluid alpha-synuclein seed amplification assay","volume":"20","author":"Bellomo","year":"2024","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.ebiom.2025.105866_bib13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S1474-4422(23)00405-2","article-title":"A biological definition of neuronal \u03b1-synuclein disease: towards an integrated staging system for research","volume":"23","author":"Simuni","year":"2024","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S1474-4422(23)00404-0","article-title":"A biological classification of Parkinson's disease: the SynNeurGe research diagnostic criteria","volume":"23","author":"H\u00f6glinger","year":"2024","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib15","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S1474-4422(08)70117-0","article-title":"Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study","volume":"7","author":"Healy","year":"2008","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ymgme.2003.11.004","article-title":"Glucocerebrosidase mutations in subjects with parkinsonism","volume":"81","author":"Lwin","year":"2004","journal-title":"Mol Genet Metab"},{"key":"10.1016\/j.ebiom.2025.105866_bib17","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1001\/jamaneurol.2017.4019","article-title":"Progression in the LRRK2-associated Parkinson disease population","volume":"75","author":"Saunders-Pullman","year":"2018","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib18","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1001\/jamaneurol.2016.2245","article-title":"Association of GBA mutations and the E326K polymorphism with motor and cognitive progression in Parkinson disease","volume":"73","author":"Davis","year":"2016","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib19","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/cpt.1634","article-title":"Development of a disease progression model for leucine-rich repeat kinase 2 in Parkinson's disease to inform clinical trial designs","volume":"107","author":"Ahamadi","year":"2020","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.ebiom.2025.105866_bib20","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/cpt.2277","article-title":"A disease progression model to quantify the nonmotor symptoms of Parkinson's disease in participants with leucine-rich repeat kinase 2 mutation","volume":"110","author":"Ahamadi","year":"2021","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.ebiom.2025.105866_bib21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S1474-4422(23)00109-6","article-title":"Assessment of heterogeneity among participants in the Parkinson's progression markers initiative cohort using \u03b1-synuclein seed amplification: a cross-sectional study","volume":"22","author":"Siderowf","year":"2023","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib22","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1002\/acn3.644","article-title":"The Parkinson's progression markers initiative (PPMI)\u2014establishing a PD biomarker cohort","volume":"5","author":"Marek","year":"2018","journal-title":"Ann Clin Transl Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1474-4422(19)30319-9","article-title":"Clinical and DAT imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study","volume":"19","author":"Simuni","year":"2020","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib24","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1002\/mds.22340","article-title":"Movement disorder society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results: MDS-UPDRS: clinimetric assessment","volume":"23","author":"Goetz","year":"2008","journal-title":"Mov Disord"},{"key":"10.1016\/j.ebiom.2025.105866_bib25","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc"},{"key":"10.1016\/j.ebiom.2025.105866_bib26","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1212\/WNL.55.10.1540","article-title":"A multicenter assessment of dopamine transporter imaging with DOPASCAN\/SPECT in parkinsonism","volume":"55","year":"2000","journal-title":"Neurology"},{"key":"10.1016\/j.ebiom.2025.105866_bib27","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/j.parkreldis.2015.10.006","article-title":"Minimal clinically important difference on the motor examination part of MDS-UPDRS","volume":"21","author":"Horv\u00e1th","year":"2015","journal-title":"Parkinsonism Relat Disord"},{"key":"10.1016\/j.ebiom.2025.105866_bib28","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/s41596-022-00787-3","article-title":"Seed Amplification Assay (SAA) for detection of pathologic \u03b1Synuclein aggregates in CSF as biomarker for Parkinson's disease and related synucleinopathies","volume":"18","author":"Concha-Marambio","year":"2023","journal-title":"Nat Protoc"},{"key":"10.1016\/j.ebiom.2025.105866_bib29","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/S1474-4422(24)00395-8","article-title":"Sensitivity and specificity of a seed amplification assay for diagnosis of multiple system atrophy: a multicentre cohort study","volume":"23","author":"Ma","year":"2024","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib30","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10654-019-00494-6","article-title":"Principles of confounder selection","volume":"15","author":"VanderWeele","year":"2019","journal-title":"Eur J Epidemiol"},{"key":"10.1016\/j.ebiom.2025.105866_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.bpc.2020.106534","article-title":"The interplay between Glucocerebrosidase, \u03b1-synuclein and lipids in human models of Parkinson's disease","volume":"273","author":"Munoz","year":"2021","journal-title":"Biophys Chem"},{"key":"10.1016\/j.ebiom.2025.105866_bib32","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1001\/jamaneurol.2014.2704","article-title":"Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease","volume":"72","author":"Kalia","year":"2015","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40478-018-0508-2","article-title":"Rapid and ultra-sensitive quantitation of disease-associated \u03b1-synuclein seeds in brain and cerebrospinal fluid by \u03b1Syn RT-QuIC","volume":"6","author":"Groveman","year":"2018","journal-title":"Acta Neuropathol Commun"},{"key":"10.1016\/j.ebiom.2025.105866_bib34","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/acn3.51280","article-title":"A rapid \u03b1-synuclein seed assay of Parkinson's disease CSF panel shows high diagnostic accuracy","volume":"8","author":"Orru","year":"2021","journal-title":"Ann Clin Transl Neurol"},{"key":"10.1016\/j.ebiom.2025.105866_bib35","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1021\/acs.jpcb.2c08326","article-title":"Quantitative seed amplification assay: a proof-of-principle study","volume":"127","author":"Vaneyck","year":"2023","journal-title":"J Phys Chem B"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S235239642500310X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S235239642500310X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T17:39:56Z","timestamp":1772905196000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S235239642500310X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":35,"alternative-id":["S235239642500310X"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2025.105866","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Baseline \u03b1-synuclein seeding activity and disease progression in sporadic and genetic Parkinson's disease in the PPMI cohort","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2025.105866","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"105866"}}