{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:11:11Z","timestamp":1792228271183,"version":"4.4.0"},"reference-count":153,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroaxonal damage underlies permanent disability in various neurological conditions, both neuroautoimmune and neurodegenerative. It is crucial to accurately quantify and monitor axonal injury using biomarkers to evaluate disease progression and treatment effectiveness and offer prognostic insights. Neurofilaments (NFs), and especially neurofilament light chain (NfL), show promise for this purpose, as their levels increase with neuroaxonal damage in both cerebrospinal fluid and blood, independent of specific causal pathways. Recent advances in ultrasensitive immunoassays enable the reliable detection of NFs in blood, transforming them from research tools into clinically applicable measures. In multiple sclerosis (MS), serum NfL correlates with disease activity, treatment response, and long-term disability, and may complement MRI in monitoring subclinical progression. In MS, NfL is primarily emerging as a marker of disease activity and treatment response; in amyotrophic lateral sclerosis (ALS), it has progressed further, being integrated into clinical trials as a pharmacodynamic endpoint and considered by regulatory agencies as a drug development tool. Additionally, NFs are increasingly being investigated in Alzheimer\u2019s disease, frontotemporal dementia, and other neurodegenerative disorders, though their disease specificity is limited. Ongoing challenges include older and novel assay harmonization, normative range interpretation, biological and analytical variability, and integration with other molecular and imaging biomarkers. This critical narrative review synthesizes the existing literature on NFs as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers and discusses their role in therapeutic development and precision medicine in neuroautoimmune and neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms26199739","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:48:07Z","timestamp":1759834087000},"page":"9739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Neurofilament Biomarkers in Neurology: From Neuroinflammation to Neurodegeneration, Bridging Established and Novel Analytical Advances with Clinical Practice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-858X","authenticated-orcid":false,"given":"Ariadne","family":"Daponte","sequence":"first","affiliation":[{"name":"Neuromuscular Diseases Unit, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5806-0717","authenticated-orcid":false,"given":"Christos","family":"Koros","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases and Rare Dementias Unit, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-2799","authenticated-orcid":false,"given":"Charalampos","family":"Skarlis","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Demyelinating Diseases Unit, Center of Expertise for Rare Demyelinating and Autoinflammatory Diseases of CNS, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7362-9610","authenticated-orcid":false,"given":"Daphne","family":"Siozios","sequence":"additional","affiliation":[{"name":"Medical Degree English Program, Athens School of Medicine, National and Kapodistrian University of Athens (NKUA), 10679 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Rentzos","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8863-3635","authenticated-orcid":false,"given":"Sokratis G.","family":"Papageorgiou","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases and Rare Dementias Unit, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-670X","authenticated-orcid":false,"given":"Maria","family":"Anagnostouli","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis and Demyelinating Diseases Unit, Center of Expertise for Rare Demyelinating and Autoinflammatory Diseases of CNS, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aeginition University Hospital, Vas. Sofias 72-74, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13024-020-00406-3","article-title":"Neurofilaments in Motor Neuron Disorders: Towards Promising Diagnostic and Prognostic Biomarkers","volume":"15","author":"Zucchi","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a018309","DOI":"10.1101\/cshperspect.a018309","article-title":"Neurofilaments and Neurofilament Proteins in Health and Disease","volume":"9","author":"Yuan","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Verde, F., Otto, M., and Silani, V. (2021). Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Front. 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