{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:14:09Z","timestamp":1791227649460,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neuroaxonal injury is a major driver of irreversible disability in demyelinating conditions. Accurate assessment of the association between demyelination and axonal pathology is critical for evaluating and developing effective therapeutic approaches. Measuring neurofilament light chain (NfL) in the blood could putatively allow longitudinal monitoring of neuroaxonal injury at \u2018single protein resolution\u2019 with high pathological specificity. Here, we demonstrate a robust association between blood and tissue NfL-based assessment of neuroaxonal injury and severity of inflammatory demyelination in experimental autoimmune encephalitis (EAE).<\/jats:p>\n               <jats:p>In EAE, high levels of NfL were evident at the peak of demyelination and correlated with tissue evidence of NfL loss when using antibodies that target the same NfL epitopes. In addition, we validate the longitudinal NfL dynamics in relation to de- and remyelination in an inducible genetic model of inflammatory-independent myelin loss. Through inducible knockout of myelin regulatory factor (Myrf) in proteolipid protein (PLP) expressing cells in Myrffl\/fl PLP1-CreERT (Myrf\u0394iPLP) mice, serum NfL peaked at the time of demyelination and reduced following effective remyelination. In people with multiple sclerosis, the most common demyelinating condition, we confirmed the association between NfL and myelin breakdown proteins in two independent cohorts using Olink proximity extension assays, the ReBUILD clinical trial and the multiple sclerosis participants in the UK-Biobank.<\/jats:p>\n               <jats:p>Our study provides a translational framework to understand the biology behind NfL changes in the context of de- and remyelination and reveals novel aspects related to monitoring potentially reversible neuroaxonal pathology in humans and rodents.<\/jats:p>","DOI":"10.1093\/brain\/awaf144","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:41:50Z","timestamp":1745577710000},"page":"3011-3020","source":"Crossref","is-referenced-by-count":17,"title":["Markers of axonal injury in blood and tissue triggered by acute and chronic demyelination"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-4169","authenticated-orcid":false,"given":"Ahmed","family":"Abdelhak","sequence":"first","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Cordano","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]},{"name":"Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova , Genova 16132 ,","place":["Italy"]},{"name":"IRCCS Ospedale Policlinico San Martino , Genova 16132 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg J","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University , Portland, OR 97239 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Emberley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University , Portland, OR 97239 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Nocera","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirtana","family":"Ananth","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"Jabassini","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiarra","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette","family":"Reinsberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-5983","authenticated-orcid":false,"given":"Frederike Cosima","family":"Oertel","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center, Charit\u00e9-Universit\u00e4tsmedizin , Berlin 13125 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Beaudry-Richard","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6963-8892","authenticated-orcid":false,"given":"Jens","family":"Kuhle","sequence":"additional","affiliation":[{"name":"Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, Multiple Sclerosis Centre, Neurology, University Hospital Basel and University of Basel , Basel 4031 ,","place":["Switzerland"]},{"name":"Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel , Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-9749","authenticated-orcid":false,"given":"Axel","family":"Petzold","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust , London EC1V 2PD ,","place":["UK"]},{"name":"UCL Institute of Ophthalmology , London EC1V 9EL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen J","family":"Patel","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust , London EC1V 2PD ,","place":["UK"]},{"name":"UCL Institute of Ophthalmology , London EC1V 9EL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana P","family":"Ribeiro Reis","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust , London EC1V 2PD ,","place":["UK"]},{"name":"UCL Institute of Ophthalmology , London EC1V 9EL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Foster","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust , London EC1V 2PD ,","place":["UK"]},{"name":"UCL Institute of Ophthalmology , London EC1V 9EL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2176-1242","authenticated-orcid":false,"given":"Jonah R","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Emery","sequence":"additional","affiliation":[{"name":"Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University , Portland, OR 97239 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari J","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]},{"name":"Department of Ophthalmology, University of California at San Francisco (UCSF) , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"2025080112525218200_awaf144-B1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41582-024-00955-x","article-title":"Neurofilaments as biomarkers in neurological disorders\u2014Towards clinical application","volume":"20","author":"Khalil","year":"2024","journal-title":"Nat Rev 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amyloidosis","volume":"96","author":"Ticau","year":"2021","journal-title":"Neurology."},{"key":"2025080112525218200_awaf144-B5"},{"key":"2025080112525218200_awaf144-B6","doi-asserted-by":"crossref","first-page":"fcad067","DOI":"10.1093\/braincomms\/fcad067","article-title":"Uman-type neurofilament light antibodies are effective reagents for the imaging of neurodegeneration","volume":"5","author":"Shaw","year":"2023","journal-title":"Brain Commun"},{"key":"2025080112525218200_awaf144-B7","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1016\/S0140-6736(17)32346-2","article-title":"Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): A randomised, controlled, double-blind, crossover trial","volume":"390","author":"Green","year":"2017","journal-title":"Lancet."},{"key":"2025080112525218200_awaf144-B8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/brain\/awx312","article-title":"Clemastine rescues myelination defects and promotes 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with multiple sclerosis","volume":"93","author":"Abdelhak","year":"2022","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"2025080112525218200_awaf144-B12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/gene.10154","article-title":"Inducible site-specific recombination in myelinating cells","volume":"35","author":"Doerflinger","year":"2003","journal-title":"Genesis"},{"key":"2025080112525218200_awaf144-B13","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","article-title":"Plasma proteomic associations with genetics and health in the UK biobank","volume":"622","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"2025080112525218200_awaf144-B14","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/acn3.51662","article-title":"Remyelination varies between and within lesions in multiple sclerosis following bexarotene","volume":"9","author":"Brown","year":"2022","journal-title":"Ann Clin Transl 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