{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:20:33Z","timestamp":1791350433512,"version":"4.3.1"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Serum neurofilament light chain (sNfL) is an analytically robust blood-based biomarker of recent neuroaxonal injury in multiple sclerosis (MS), supported by validated ultrasensitive immunoassays suitable for routine measurement. These assays now enable reliable measurement in routine care, and evidence links higher levels and rising trajectories to inflammatory activity, treatment response, and\u2014at a population level\u2014future tissue loss and disability risk. Clinical implementation is constrained by overinterpretation of single measurements: sNfL is not MS-specific, is strongly age-dependent, is influenced by systemic and neurological confounders, and reflects injury over weeks to months rather than cumulative neurodegeneration. This review proposes a clinically oriented framework in which sNfL serves as decision support alongside MRI and clinical assessment, not as a stand-alone trigger for therapy changes. We prioritize longitudinal interpretation anchored to an individual baseline or nadir, the use of age-adjusted reference frameworks (percentiles or Z-scores where available), standardization of key pre-analytical and analytical conditions, and structured approaches to discordance between biomarkers, imaging, and symptoms. We discuss the complementary role of serum glial fibrillary acidic protein (sGFAP) as a marker of chronic astroglial pathology and progression-dominant biology, and how combined biomarker patterns may refine interpretation when disability worsens despite limited inflammatory activity. Across the MS continuum\u2014from prodromal states and radiologically isolated syndrome to relapsing and progressive phenotypes\u2014we summarize practical use cases, limitations, and safety-critical \u201cred flags\u201d where marked sNfL surges warrant urgent reassessment. Finally, we highlight consensus-based implementation principles and research priorities, including pragmatic trials to test whether biomarker-informed strategies improve patient-relevant outcomes.<\/jats:p>","DOI":"10.3389\/fneur.2026.1815022","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:48:11Z","timestamp":1782276491000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Serum neurofilament light chain in multiple sclerosis: from biological signal to clinically informed decision-making"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana Bel\u00e9n","family":"Caminero","sequence":"first","affiliation":[{"name":"Department of Neurology, Complejo Asistencial de \u00c1vila","place":["\u00c1vila, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research of Malaga (IBIMA), Regional University Hospital of Malaga","place":["Malaga, Spain"]},{"name":"Department of Pharmacology and Pediatrics, Faculty of Medicine, University of Malaga","place":["Malaga, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple Sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1177\/13524585241234783","article-title":"Efficacy and safety results after >3.5 years of treatment with the Bruton's tyrosine kinase inhibitor evobrutinib 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