{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:55:46Z","timestamp":1790927746079,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Colony-stimulating factor 1 receptor (\n                      <jats:italic>CSF1R<\/jats:italic>\n                      )-related leukoencephalopathy (CRL) is a rare microgliopathy, characterized by progressive neurodegeneration. Impaired\n                      <jats:italic>STAT3<\/jats:italic>\n                      signaling reduces microglial numbers and limits their ability to clear cellular debris, leading to persistent inflammation and brain tissue damage that activates peripheral CD20\u207a B cells. These cells migrate into the CNS and secrete interleukin-6 (IL-6), amplifying inflammation and further disrupting STAT3 signaling in a self-reinforcing cycle that drives white-matter injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We describe two siblings from a single family, both carrying the same heterozygous\n                      <jats:italic>CSF1R<\/jats:italic>\n                      variant (c.2562\u2009T\u2009&gt;\u2009A, p.Asn854Lys), who received four infusions of rituximab (RTX;500\u2009mg) on a compassionate, off-label basis between 2014-2017. The long-term disease trajectory was evaluated using standardized clinical rating scales and brain magnetic resonance imaging (MRI). As a secondary biomarker outcome, serum and CSF neurofilament light chain (NfL) concentrations were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In both siblings, RTX exposure was followed by EDSS stability at 6.5 and 7.0, respectively, over 5 years, with mixed trajectories in other functional and cognitive domains. Over the 23-year MRI follow-up period, patients developed cerebral atrophy. During the post-treatment period, no new focal lesions were observed on brain MRI, and levels of CSF-NfL and CSF-CXCL13 were normalized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this preliminary familial case series of two siblings carrying the same\n                      <jats:italic>CSF1R<\/jats:italic>\n                      variant, RTX exposure was followed by long-term clinical stability and favorable biomarker trajectories. Patient 1 had a pre-treatment disease course of approximately 13 years, indicating an inherently slow disease progression that cannot be entirely separated from the treatment effect in an uncontrolled observation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-026-01936-5","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:42:22Z","timestamp":1790923342000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term clinical and biomarker observations following rituximab exposure in two siblings with CSF1R-related leukoencephalopathy: a preliminary familial case series"],"prefix":"10.1038","volume":"6","author":[{"given":"Ramojus","family":"Balevicius","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidija Marija","family":"Smertinaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourad","family":"Kourie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Wszolek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goda-Camile","family":"Mickeviciute","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4990-509X","authenticated-orcid":false,"given":"Robert","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-1022","authenticated-orcid":false,"given":"Tobias","family":"Granberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezda","family":"Zhuravleva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-3275","authenticated-orcid":false,"given":"Jinming","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7166-8951","authenticated-orcid":false,"given":"Virginija Danylaite","family":"Karrenbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"1936_CR1","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/ng.1027","volume":"44","author":"R Rademakers","year":"2011","unstructured":"Rademakers, R. et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat. Genet. 44, 200\u2013205 (2011).","journal-title":"Nat. Genet."},{"key":"1936_CR2","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1038\/s41590-025-02195-7","volume":"26","author":"S Du","year":"2025","unstructured":"Du, S. et al. Mutations in the human CSF1R gene impact microglia\u2019s maintenance of brain white matter integrity. Nat. Immunol. 26, 1198\u20131211 (2025).","journal-title":"Nat. Immunol."},{"key":"1936_CR3","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.3389\/fimmu.2019.02199","volume":"10","author":"C Easley-Neal","year":"2019","unstructured":"Easley-Neal, C., Foreman, O., Sharma, N., Zarrin, A. A. & Weimer, R. M. CSF1R ligands IL-34 and CSF1 are differentially required for microglia development and maintenance in white and gray matter brain regions. Front. Immunol. 10, 2199 (2019).","journal-title":"Front. Immunol."},{"key":"1936_CR4","doi-asserted-by":"publisher","first-page":"106566","DOI":"10.1016\/j.phrs.2022.106566","volume":"187","author":"C Xiang","year":"2023","unstructured":"Xiang, C., Li, H. & Tang, W. Targeting CSF-1R represents an effective strategy in modulating inflammatory diseases. Pharm. Res. 187, 106566 (2023).","journal-title":"Pharm. Res."},{"key":"1936_CR5","doi-asserted-by":"publisher","first-page":"8150","DOI":"10.1073\/pnas.0501643102","volume":"102","author":"L Liu","year":"2005","unstructured":"Liu, L., McBride, K. M. & Reich, N. C. STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-alpha3. Proc. Natl. Acad. Sci. USA 102, 8150\u20138155 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1936_CR6","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s40478-024-01853-5","volume":"12","author":"J Pan","year":"2024","unstructured":"Pan, J. et al. Deciphering glial contributions to CSF1R-related disorder via single-nuclear transcriptomic profiling: a case study. Acta Neuropathol. Commun. 12, 139 (2024).","journal-title":"Acta Neuropathol. Commun."},{"key":"1936_CR7","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1007\/s12264-023-01034-9","volume":"39","author":"Y Sun","year":"2023","unstructured":"Sun, Y., Yu, H. & Guan, Y. Glia connect inflammation and neurodegeneration in multiple sclerosis. Neurosci. Bull. 39, 466\u2013478 (2023).","journal-title":"Neurosci. Bull."},{"key":"1936_CR8","doi-asserted-by":"publisher","first-page":"966766","DOI":"10.3389\/fimmu.2022.966766","volume":"13","author":"L Jiao","year":"2022","unstructured":"Jiao, L. & Guo, S. Anti-IL-6 therapies in central nervous system inflammatory demyelinating diseases. Front. Immunol. 13, 966766 (2022).","journal-title":"Front. Immunol."},{"key":"1936_CR9","doi-asserted-by":"crossref","unstructured":"Espinoza, D.A. et al. Distinct stage-specific transcriptional states of B cells derived from human tonsillar tissue. JCI Insight 8, e155199 (2023).","DOI":"10.1172\/jci.insight.155199"},{"key":"1936_CR10","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1056\/NEJMoa0706383","volume":"358","author":"SL Hauser","year":"2008","unstructured":"Hauser, S. L. et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N. Engl. J. Med. 358, 676\u2013688 (2008).","journal-title":"N. Engl. J. Med."},{"key":"1936_CR11","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1212\/WNL.0000000000006642","volume":"91","author":"T Konno","year":"2018","unstructured":"Konno, T., Kasanuki, K., Ikeuchi, T., Dickson, D. W. & Wszolek, Z. K. CSF1R-related leukoencephalopathy: a major player in primary microgliopathies. Neurology 91, 1092\u20131104 (2018).","journal-title":"Neurology"},{"key":"1936_CR12","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1111\/ene.12572","volume":"22","author":"C Sundal","year":"2015","unstructured":"Sundal, C. et al. Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis. Eur. J. Neurol. 22, 328\u2013333 (2015).","journal-title":"Eur. J. Neurol."},{"key":"1936_CR13","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/mds.21198","volume":"22","author":"CG Goetz","year":"2007","unstructured":"Goetz, C. G. et al. Movement disorder society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): process, format, and clinimetric testing plan. Mov. Disord. 22, 41\u201347 (2007).","journal-title":"Mov. Disord."},{"key":"1936_CR14","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1212\/WNL.17.5.427","volume":"17","author":"MM Hoehn","year":"1967","unstructured":"Hoehn, M. M. & Yahr, M. D. Parkinsonism: onset, progression and mortality. Neurology 17, 427\u2013442 (1967).","journal-title":"Neurology"},{"key":"1936_CR15","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/S0022-510X(99)00210-5","volume":"169","author":"JM Cedarbaum","year":"1999","unstructured":"Cedarbaum, J. M. et al. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J. Neurol. Sci. 169, 13\u201321 (1999).","journal-title":"J. Neurol. Sci."},{"key":"1936_CR16","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1017\/S0033291796004382","volume":"27","author":"P Spinhoven","year":"1997","unstructured":"Spinhoven, P. et al. A validation study of the Hospital Anxiety and Depression Scale (HADS) in different groups of Dutch subjects. Psychol. Med. 27, 363\u2013370 (1997).","journal-title":"Psychol. Med."},{"key":"1936_CR17","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","volume":"33","author":"JF Kurtzke","year":"1983","unstructured":"Kurtzke, J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33, 1444\u20131452 (1983).","journal-title":"Neurology"},{"key":"1936_CR18","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/j.1532-5415.1992.tb01992.x","volume":"40","author":"TN Tombaugh","year":"1992","unstructured":"Tombaugh, T. N. & McIntyre, N. J. The mini-mental state examination: a comprehensive review. J. Am. Geriatr. Soc. 40, 922\u2013935 (1992).","journal-title":"J. Am. Geriatr. Soc."},{"key":"1936_CR19","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1177\/1352458518808204","volume":"25","author":"L Strober","year":"2019","unstructured":"Strober, L. et al. Symbol Digit Modalities Test: a valid clinical trial endpoint for measuring cognition in multiple sclerosis. Mult. Scler. 25, 1781\u20131790 (2019).","journal-title":"Mult. Scler."},{"key":"1936_CR20","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1093\/brain\/124.5.962","volume":"124","author":"J Hobart","year":"2001","unstructured":"Hobart, J., Lamping, D., Fitzpatrick, R., Riazi, A. & Thompson, A. The multiple sclerosis impact scale (MSIS-29): a new patient-based outcome measure. Brain J. Neurol. 124, 962\u2013973 (2001).","journal-title":"Brain J. Neurol."},{"key":"1936_CR21","first-page":"155","volume":"78","author":"G Balestroni","year":"2012","unstructured":"Balestroni, G. & Bertolotti, G. EuroQol-5D (EQ-5D): an instrument for measuring quality of life. Monaldi Arch. Chest Dis. 78, 155\u2013159 (2012).","journal-title":"Monaldi Arch. Chest Dis."},{"key":"1936_CR22","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/ane.13589","volume":"145","author":"I Rosenstein","year":"2022","unstructured":"Rosenstein, I. et al. Four Swedish cases of CSF1R-related leukoencephalopathy: visualization of clinical phenotypes. Acta Neurol. Scand. 145, 599\u2013609 (2022).","journal-title":"Acta Neurol. Scand."},{"key":"1936_CR23","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ebiom.2015.11.036","volume":"3","author":"M Gissl\u00e9n","year":"2016","unstructured":"Gissl\u00e9n, M. et al. Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine 3, 135\u2013140 (2016).","journal-title":"EBioMedicine"},{"key":"1936_CR24","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 17, 405\u2013424 (2015).","journal-title":"Genet Med."},{"key":"1936_CR25","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/S1474-4422(22)00009-6","volume":"21","author":"P Benkert","year":"2022","unstructured":"Benkert, P. et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol. 21, 246\u2013257 (2022).","journal-title":"Lancet Neurol."},{"key":"1936_CR26","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1111\/jon.12725","volume":"30","author":"G Mangeat","year":"2020","unstructured":"Mangeat, G. et al. Machine learning and multiparametric brain MRI to differentiate hereditary diffuse leukodystrophy with spheroids from multiple sclerosis. J. Neuroimaging 30, 674\u2013682 (2020).","journal-title":"J. Neuroimaging"},{"key":"1936_CR27","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.3174\/ajnr.A4665","volume":"37","author":"T Granberg","year":"2016","unstructured":"Granberg, T. et al. Clinical feasibility of synthetic MRI in multiple sclerosis: a diagnostic and volumetric validation study. AJNR Am. J. Neuroradiol. 37, 1023\u20131029 (2016).","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"1936_CR28","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","volume":"310","author":"A World Medical","year":"2013","unstructured":"World Medical, A. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310, 2191\u20132194 (2013).","journal-title":"JAMA"},{"key":"1936_CR29","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/ana.1032","volume":"50","author":"WI McDonald","year":"2001","unstructured":"McDonald, W. I. et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. 50, 121\u2013127 (2001).","journal-title":"Ann. Neurol."},{"key":"1936_CR30","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/ene.13464","volume":"25","author":"T Konno","year":"2018","unstructured":"Konno, T. et al. Diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation. Eur. J. Neurol. 25, 142\u2013147 (2018).","journal-title":"Eur. J. Neurol."},{"key":"1936_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2025.107133","volume":"216","author":"A Ajoolabady","year":"2025","unstructured":"Ajoolabady, A. et al. Dual role of microglia in neuroinflammation and neurodegenerative diseases. Neurobiol. Dis. 216, 107133 (2025).","journal-title":"Neurobiol. Dis."},{"key":"1936_CR32","doi-asserted-by":"publisher","first-page":"16975","DOI":"10.1073\/pnas.1315862110","volume":"110","author":"Y Wang","year":"2013","unstructured":"Wang, Y., van Boxel-Dezaire, A. H. H., Cheon, H., Yang, J. & Stark, G. R. STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor. Proc. Natl. Acad. Sci. USA 110, 16975\u201316980 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1936_CR33","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70422","volume":"31","author":"T Yu","year":"2025","unstructured":"Yu, T. et al. Blood-Brain Barrier (BBB) dysfunction in CNS diseases: paying attention to pericytes. CNS Neurosci. Ther. 31, e70422 (2025).","journal-title":"CNS Neurosci. Ther."},{"key":"1936_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13812-z","volume":"10","author":"K Haruwaka","year":"2019","unstructured":"Haruwaka, K. et al. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat. Commun. 10, 5816 (2019).","journal-title":"Nat. Commun."},{"key":"1936_CR35","first-page":"321","volume":"23","author":"XM Chen","year":"2019","unstructured":"Chen, X. M., Yu, Y. H., Wang, L., Zhao, X. Y. & Li, J. R. Effect of the JAK2\/STAT3 signaling pathway on nerve cell apoptosis in rats with white matter injury. Eur. Rev. Med Pharm. Sci. 23, 321\u2013327 (2019).","journal-title":"Eur. Rev. Med Pharm. Sci."},{"key":"1936_CR36","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1038\/s41380-019-0471-8","volume":"25","author":"GM Wittenberg","year":"2020","unstructured":"Wittenberg, G. M. et al. Effects of immunomodulatory drugs on depressive symptoms: a mega-analysis of randomized, placebo-controlled clinical trials in inflammatory disorders. Mol. Psychiatry 25, 1275\u20131285 (2020).","journal-title":"Mol. Psychiatry"},{"key":"1936_CR37","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1136\/svn-2021-001028","volume":"7","author":"ZV Zheng","year":"2022","unstructured":"Zheng, Z. V. et al. Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage. Stroke Vasc. Neurol. 7, 62\u201370 (2022).","journal-title":"Stroke Vasc. Neurol."},{"key":"1936_CR38","doi-asserted-by":"publisher","first-page":"1103416","DOI":"10.3389\/fneur.2023.1103416","volume":"14","author":"J Qin","year":"2023","unstructured":"Qin, J., Ma, Z., Chen, X. & Shu, S. Microglia activation in central nervous system disorders: a review of recent mechanistic investigations and development efforts. Front. Neurol. 14, 1103416 (2023).","journal-title":"Front. Neurol."},{"key":"1936_CR39","doi-asserted-by":"publisher","first-page":"636","DOI":"10.3389\/fimmu.2015.00636","volume":"6","author":"L Michel","year":"2015","unstructured":"Michel, L. et al. B cells in the multiple sclerosis central nervous system: trafficking and contribution to CNS-compartmentalized inflammation. Front. Immunol. 6, 636 (2015).","journal-title":"Front. Immunol."},{"key":"1936_CR40","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.789834","volume":"13","author":"B Hu","year":"2021","unstructured":"Hu, B. et al. Insights into the role of CSF1R in the central nervous system and neurological disorders. Front. Aging Neurosci. 13, 789834 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"1936_CR41","doi-asserted-by":"crossref","unstructured":"Toral-Rios, D. et al. Activation of STAT3 regulates reactive astrogliosis and neuronal death induced by A\u03b2O neurotoxicity. Int. J. Mol. Sci. 21, 7458 (2020).","DOI":"10.3390\/ijms21207458"},{"key":"1936_CR42","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/wdev.176","volume":"4","author":"DM Ornitz","year":"2015","unstructured":"Ornitz, D. M. & Itoh, N. The Fibroblast Growth Factor signaling pathway. WIREs Dev. Biol. 4, 215\u2013266 (2015).","journal-title":"WIREs Dev. Biol."},{"key":"1936_CR43","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s40478-025-02028-6","volume":"13","author":"R Kushwaha","year":"2025","unstructured":"Kushwaha, R., Molesworth, K., Makarava, N. & Baskakov, I. V. Downregulation of STAT3 transcription factor reverses synaptotoxic phenotype of reactive astrocytes associated with prion diseases. Acta Neuropathol. Commun. 13, 101 (2025).","journal-title":"Acta Neuropathol. Commun."}],"container-title":["Communications Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s43856-026-01936-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43856-026-01936-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43856-026-01936-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:29:45Z","timestamp":1790926185000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s43856-026-01936-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1936"],"URL":"https:\/\/doi.org\/10.1038\/s43856-026-01936-5","relation":{},"ISSN":["2730-664X"],"issn-type":[{"value":"2730-664X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"assertion":[{"value":"15 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Z.K.W. is partially supported by the NIH\/NIA and NIH\/NINDS, the Haworth Family Professorship in Neurodegenerative Diseases fund, The Albertson Parkinson\u2019s Research Foundation, PPND Family Foundation, and the gifts from the Valerie Shapiro & Jordan Russell Family and from Houlihan Lokey, Inc, from the Margaret N. and John Wilchek Family, and from the Donald G. and Jodi P. Heeringa Family. He serves as the Mayo Clinic site PI on ONO-2808-03 project; as Co-PI of the Mayo Clinic APDA Center for Advanced Research; and as an external advisory board member for the Savanna Biotherapeutics, Inc. and as a consultant for the BlueRock Therapeutics LP.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"514"}}