{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:04:18Z","timestamp":1793070258322,"version":"4.5.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["HT94252310499"],"award-info":[{"award-number":["HT94252310499"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Multiple Sclerosis Society","id":[{"id":"https:\/\/ror.org\/03019wv17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Valhalla Foundation, Westridge Foundation, Water Cove Charitable Foundation","id":[{"id":"https:\/\/ror.org\/01v231v33","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Valhalla Foundation, Westridge Foundation","id":[{"id":"https:\/\/ror.org\/01v231v33","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1038\/s41591-025-04014-w","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:03:20Z","timestamp":1760951000000},"page":"362-368","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-4169","authenticated-orcid":false,"given":"Ahmed","family":"Abdelhak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Cerono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahime","family":"Sheikhzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Harroud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4433-4087","authenticated-orcid":false,"given":"Kiarra","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-1388","authenticated-orcid":false,"given":"Colin R.","family":"Zamecnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2089-8116","authenticated-orcid":false,"given":"Gavin M.","family":"Sowa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-9526","authenticated-orcid":false,"given":"John","family":"Boscardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-0442","authenticated-orcid":false,"given":"Christian","family":"Cordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asritha","family":"Tubati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Fouassier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8079-918X","authenticated-orcid":false,"given":"Eric D.","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Refujia","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9816-5932","authenticated-orcid":false,"given":"Adam","family":"Santaniello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-2137","authenticated-orcid":false,"given":"Kelsey C.","family":"Zorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6572-7962","authenticated-orcid":false,"given":"Jill A.","family":"Hollenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge R.","family":"Oksenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7689-2533","authenticated-orcid":false,"given":"Bruce A. C.","family":"Cree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4932-4001","authenticated-orcid":false,"given":"Stephen L.","family":"Hauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2176-1242","authenticated-orcid":false,"given":"Jonah R.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0067-194X","authenticated-orcid":false,"given":"Sergio E.","family":"Baranzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-5714","authenticated-orcid":false,"given":"Mitchell T.","family":"Wallin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8705-5084","authenticated-orcid":false,"given":"Michael R.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari J.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"4014_CR1","doi-asserted-by":"crossref","unstructured":"The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol. 9, 520\u2013532 (2020).","DOI":"10.1016\/S1474-4422(10)70064-8"},{"key":"4014_CR2","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/s41591-024-02938-3","volume":"30","author":"CR Zamecnik","year":"2024","unstructured":"Zamecnik, C. R. et al. An autoantibody signature predictive for multiple sclerosis. Nat. Med. 30, 1300\u20131308 (2024).","journal-title":"Nat. Med."},{"key":"4014_CR3","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1126\/science.abj8222","volume":"375","author":"K Bjornevik","year":"2022","unstructured":"Bjornevik, K. et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 375, 296\u2013301 (2022).","journal-title":"Science"},{"key":"4014_CR4","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s41586-022-04432-7","volume":"603","author":"TV Lanz","year":"2022","unstructured":"Lanz, T. V. et al. Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Nature 603, 321\u2013327 (2022).","journal-title":"Nature"},{"key":"4014_CR5","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/s41582-021-00519-3","volume":"17","author":"N Makhani","year":"2021","unstructured":"Makhani, N. & Tremlett, H. The multiple sclerosis prodrome. Nat. Rev. Neurol. 17, 515\u2013521 (2021).","journal-title":"Nat. Rev. Neurol."},{"key":"4014_CR6","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1002\/ana.24769","volume":"80","author":"M Cortese","year":"2016","unstructured":"Cortese, M. et al. Preclinical disease activity in multiple sclerosis: a prospective study of cognitive performance prior to first symptom. Ann. Neurol. 80, 616\u2013624 (2016).","journal-title":"Ann. Neurol."},{"key":"4014_CR7","first-page":"1542","volume":"41","author":"M Hosseiny","year":"2020","unstructured":"Hosseiny, M., Newsome, S. D. & Yousem, D. M. Radiologically isolated syndrome: a review for neuroradiologists. AJNR Am. J. Neuroradiol. 41, 1542\u20131549 (2020).","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"4014_CR8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1001\/jamaneurol.2019.3238","volume":"77","author":"K Bjornevik","year":"2020","unstructured":"Bjornevik, K. et al. Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis. JAMA Neurol. 77, 58\u201364 (2020).","journal-title":"JAMA Neurol."},{"key":"4014_CR9","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","volume":"14","author":"M Khalil","year":"2018","unstructured":"Khalil, M. et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 14, 577\u2013589 (2018).","journal-title":"Nat. Rev. Neurol."},{"key":"4014_CR10","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200335","volume":"12","author":"J Britze","year":"2025","unstructured":"Britze, J. et al. Temporal dynamics of plasma neurofilament light in blood donors with preclinical multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 12, e200335 (2025).","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"4014_CR11","first-page":"325","volume":"95","author":"D Jons","year":"2024","unstructured":"Jons, D. et al. Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage. J. Neurol. Neurosurg. Psychiatry 95, 325\u2013332 (2024).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"4014_CR12","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1016\/j.immuni.2023.04.013","volume":"56","author":"MG Kiss","year":"2023","unstructured":"Kiss, M. G. et al. Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis. Immunity 56, 1502\u20131514 (2023).","journal-title":"Immunity"},{"key":"4014_CR13","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.molmed.2013.08.001","volume":"19","author":"C Mc Guire","year":"2013","unstructured":"Mc Guire, C., Prinz, M., Beyaert, R. & van Loo, G. Nuclear factor kappa B (NF-kappaB) in multiple sclerosis pathology. Trends Mol. Med. 19, 604\u2013613 (2013).","journal-title":"Trends Mol. Med."},{"key":"4014_CR14","doi-asserted-by":"publisher","first-page":"a001271","DOI":"10.1101\/cshperspect.a001271","volume":"1","author":"B Kaltschmidt","year":"2009","unstructured":"Kaltschmidt, B. & Kaltschmidt, C. NF-kappaB in the nervous system. Cold Spring Harb. Perspect. Biol. 1, a001271 (2009).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"4014_CR15","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1002\/acn3.51990","volume":"11","author":"BM Jacobs","year":"2024","unstructured":"Jacobs, B. M. et al. Plasma proteomic profiles of UK Biobank participants with multiple sclerosis. Ann. Clin. Transl. Neurol. 11, 698\u2013709 (2024).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"4014_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42682-9","volume":"14","author":"J Akesson","year":"2023","unstructured":"Akesson, J. et al. Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis. Nat. Commun. 14, 6903 (2023).","journal-title":"Nat. Commun."},{"key":"4014_CR17","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202100170","volume":"22","author":"DE Haslam","year":"2022","unstructured":"Haslam, D. E. et al. Stability and reproducibility of proteomic profiles in epidemiological studies: comparing the Olink and SOMAscan platforms. Proteomics 22, e2100170 (2022).","journal-title":"Proteomics"},{"key":"4014_CR18","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf144","author":"A Abdelhak","year":"2025","unstructured":"Abdelhak, A., et al. Markers of axonal injury in blood and tissue triggered by acute and chronic demyelination. Brain https:\/\/doi.org\/10.1093\/brain\/awaf144 (2025).","journal-title":"Brain"},{"key":"4014_CR19","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adj8094","volume":"9","author":"V Kavaka","year":"2024","unstructured":"Kavaka, V. et al. Twin study identifies early immunological and metabolic dysregulation of CD8(+) T cells in multiple sclerosis. Sci. Immunol. 9, eadj8094 (2024).","journal-title":"Sci. Immunol."},{"key":"4014_CR20","doi-asserted-by":"publisher","first-page":"21546","DOI":"10.1073\/pnas.2003339117","volume":"117","author":"LA Gerdes","year":"2020","unstructured":"Gerdes, L. A. et al. Immune signatures of prodromal multiple sclerosis in monozygotic twins. Proc. Natl Acad. Sci. USA 117, 21546\u201321556 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4014_CR21","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1093\/brain\/awac092","volume":"146","author":"H Shams","year":"2023","unstructured":"Shams, H. et al. Polygenic risk score association with multiple sclerosis susceptibility and phenotype in Europeans. Brain 146, 645\u2013656 (2023).","journal-title":"Brain"},{"key":"4014_CR22","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/ana.25799","volume":"88","author":"C Lebrun-Frenay","year":"2020","unstructured":"Lebrun-Frenay, C. et al. Radiologically isolated syndrome: 10-year risk estimate of a clinical event. Ann. Neurol. 88, 407\u2013417 (2020).","journal-title":"Ann. Neurol."},{"key":"4014_CR23","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1093\/brain\/aws099","volume":"135","author":"MT Wallin","year":"2012","unstructured":"Wallin, M. T. et al. The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex and service. Brain 135, 1778\u20131785 (2012).","journal-title":"Brain"},{"key":"4014_CR24","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","volume":"17","author":"AJ Thompson","year":"2018","unstructured":"Thompson, A. J. et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 17, 162\u2013173 (2018).","journal-title":"Lancet Neurol."},{"key":"4014_CR25","doi-asserted-by":"publisher","first-page":"5473","DOI":"10.4049\/jimmunol.181.8.5473","volume":"181","author":"SJ Caillier","year":"2008","unstructured":"Caillier, S. J. et al. Uncoupling the roles of HLA-DRB1 and HLA-DRB5 genes in multiple sclerosis. J. Immunol. 181, 5473\u20135480 (2008).","journal-title":"J. Immunol."},{"key":"4014_CR26","unstructured":"Nevola, K. et al. OlinkAnalyze: facilitate analysis of proteomic data from Olink. CRAN https:\/\/CRAN.R-project.org\/package=OlinkAnalyze (2025)."},{"key":"4014_CR27","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"4014_CR28","doi-asserted-by":"publisher","unstructured":"Kuznetsova, A., Brockhoff, P. B. & Christensen, R. H. B. lmerTest package: tests in linear mixed effects models. J. Stat. Softw. 82, https:\/\/doi.org\/10.18637\/jss.v082.i13 (2017).","DOI":"10.18637\/jss.v082.i13"},{"key":"4014_CR29","unstructured":"L\u00fcdecke, D. sjPlot: data visualization for statistics in social science. CRAN https:\/\/CRAN.R-project.org\/package=sjPlot (2025)."},{"key":"4014_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09773-y","volume":"10","author":"International Multiple Sclerosis Genetics Consortium","year":"2019","unstructured":"International Multiple Sclerosis Genetics Consortium A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis. Nat. Commun. 10, 2236 (2019).","journal-title":"Nat. Commun."},{"key":"4014_CR31","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1021\/acs.jproteome.8b00702","volume":"18","author":"NT Doncheva","year":"2019","unstructured":"Doncheva, N. T., Morris, J. H., Gorodkin, J. & Jensen, L. J. Cytoscape StringApp: network analysis and visualization of proteomics data. J. Proteome Res. 18, 623\u2013632 (2019).","journal-title":"J. Proteome Res."},{"key":"4014_CR32","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498\u20132504 (2003).","journal-title":"Genome Res."},{"key":"4014_CR33","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner, M. et al. Gene ontology: tool for the unification of biology. Nat. Genet. 25, 25\u201329 (2000).","journal-title":"Nat. Genet."},{"key":"4014_CR34","doi-asserted-by":"publisher","unstructured":"Gene Ontology Consortium et al. The gene ontology knowledgebase in 2023. Genetics https:\/\/doi.org\/10.1093\/genetics\/iyad031 (2023).","DOI":"10.1093\/genetics\/iyad031"},{"key":"4014_CR35","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/nar\/27.1.29","volume":"27","author":"H Ogata","year":"1999","unstructured":"Ogata, H. et al. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res 27, 29\u201334 (1999).","journal-title":"Nucleic Acids Res"},{"key":"4014_CR36","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947\u20131951 (2019).","journal-title":"Protein Sci."},{"key":"4014_CR37","doi-asserted-by":"publisher","first-page":"D587","DOI":"10.1093\/nar\/gkac963","volume":"51","author":"M Kanehisa","year":"2023","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 51, D587\u2013D592 (2023).","journal-title":"Nucleic Acids Res."},{"key":"4014_CR38","doi-asserted-by":"publisher","first-page":"D679","DOI":"10.1093\/nar\/gkad960","volume":"52","author":"A Agrawal","year":"2024","unstructured":"Agrawal, A. et al. WikiPathways 2024: next generation pathway database. Nucleic Acids Res. 52, D679\u2013D689 (2024).","journal-title":"Nucleic Acids Res."},{"key":"4014_CR39","unstructured":"Olsen, L. groupdata2: creating groups from data. CRAN https:\/\/CRAN.R-project.org\/package=groupdata2 (2024)."},{"key":"4014_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v036.i11","volume":"36","author":"MB Kursa","year":"2010","unstructured":"Kursa, M. B. & Rudnicki, W. R. Feature selection with the Boruta package. J. Stat. Softw. 36, 1\u201313 (2010).","journal-title":"J. Stat. Softw."},{"key":"4014_CR41","doi-asserted-by":"publisher","unstructured":"Abdelhak, A., Wilson, M. R., Wallin, M., Cree, B. & Green, A. Serum proteome characterizes sequence of CNS injury in pre-symptomatic multiple sclerosis. Dryad https:\/\/doi.org\/10.5061\/dryad.fttdz093t (2025).","DOI":"10.5061\/dryad.fttdz093t"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-04014-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-04014-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-04014-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T15:03:10Z","timestamp":1769007790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-025-04014-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["4014"],"URL":"https:\/\/doi.org\/10.1038\/s41591-025-04014-w","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]},"assertion":[{"value":"2 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A preliminary patent application has been filed for a new method to diagnose presymptomatic multiple sclerosis using protein biomarker panel, as described in this study. The patent application number is 63\/750,666, filed on 28 January 2025. A.A. received consultation\/speaker fees from Roche, OctaveBio, EMD Serono and Sanofi. F.S. reports a relationship with F. Hoffmann-La Roche Ltd. that includes employment and equity or stocks. E.D.C. is a founder of Survey Genomics. A.J.G. reports research support and grants from NINDS R01 NS105741 R01AG062562 R01AG038791, NMSS RG-1707-28564, All May See, Westridge Foundation, JAMA Neurology, Roche, Pipeline Pharmaceuticals and Cognito Therapeutics. A.J.G. is also an associate editor for JAMA Neurology. S.L.H. currently serves on the scientific advisory boards of Accure, Alector, Annexon and Hinge Bio; previously consulted for BD, Gilead, Moderna, NGM Bio, Nurix Therapeutics and Pheno Therapeutics; previously served on the Board of Directors of Neurona and currently serves as an advisor. S.L.H. also has received nonfinancial support (travel reimbursement and writing support for anti-CD20-therapy-related meetings and presentations) from F. Hoffmann-La Roche and Novartis AG; and has received no personal compensation from any entity that sells or tests therapeutics for MS. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}