Neurofilament light chains in neurological disorders Review article
Article Sidebar
Published:
Nov 17, 2025
Keywords:
neurofilament light chain, biomarkers, neurodegeneration, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, stroke
Main Article Content
Abstract
Neurofilament light chain is a neuronal cytoskeletal protein whose concentration in body fluids reflects the extent of axonal injury. As a sensitive yet non-specific biomarker, it is useful in multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and stroke. Highly sensitive blood assays enable monitoring of disease activity, prediction of prognosis and assessment of treatment efficacy. This article reviews current evidence and clinical implications.
Article Details
Issue
Section
Articles
Copyright ? by Medical Education. All rights reserved.
References
1. Kwinta R, Marciniak D, Nowak-Kiczmer M et al. Neurofilament lekki w stwardnieniu rozsianym. Pol Przegl Neurolog. 2022; 18(2): 103-9.
2. Coppens S, Lehmann S, Hopley C et al. Neurofilament-Light, a Promising Biomarker: Analytical, Metrological and Clinical Challenges. Int J Mol Sci. 2023; 24(14): 11624.
3. Jung Y, Damoiseaux JS. The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer’s disease. Brain. 2024; 147(1): 12-25.
4. Shahim P, Norato G, Sinaii N et al. Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. Genes (Basel). 2024; 15(4): 496.
5. Li Y, Li F, Liu X et al. Association between serum neurofilament light chain levels and sleep disorders in patients with Parkinson’s disease. Neurosci Lett. 2023; 812: 137394.
6. Fan Z, Liu X, Liu J et al. Neurofilament Light Chain as a Potential Biomarker in Plasma for Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review and a Meta-Analysis. J Integr Neurosci. 2023; 22(4): 85.
7. Booth RA, Beriault D, Schneider R et al. Validation and generation of age-specific reference intervals for a new blood neurofilament light chain assay. Clinica Chimica Acta. 2025; 577: 120447.
8. Bar-Or A, Thanei GA, Harp C et al. Blood neurofilament light levels predict non-relapsing progression following anti-CD20 therapy in relapsing and primary progressive multiple sclerosis: findings from the ocrelizumab randomised, double-blind phase 3 clinical trials. EBioMedicine. 2023; 93: 104662.
9. Illán-Gala I, Lleo A, Karydas A et al. Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease. Neurology. 2021; 96(5): e671-83.
10. Tony AA, Kholef EFM, Elgendy DB et al. Neurofilament Light Chain Correlates with Stroke Severity and Clinical Outcome in Acute Cerebrovascular Stroke Patients. Cell Mol Neurobiol. 2025; 45(1): 39.
11. Szilasiova J, Mikula P, Rosenberger J et al. Associations between neurofilament light chain levels, disease activity and brain atrophy in progressive multiple sclerosis. Biomedical Papers. 2022; 166(3): 304-11.
12. Abdelhak A, Benkert P, Schaedelin S et al. Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis. JAMA Neurol. 2023; 80(12): 1317.
13. Kuhle J, Daizadeh N, Benkert P et al. Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing–remitting MS. Mult Scler. 2022; 28(4): 573-82.
14. Brune S, Høgestøl EA, de Rodez Benavent SA et al. Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis. Mult Scler. 2022; 28(12): 1859-70.
15. Liu N, Sun M, Zhang W et al. Prognostic value of neurofilament light chain in natalizumab therapy for different phases of multiple sclerosis: A systematic review and meta-analysis. J Clin Neurosci. 2022; 101: 198-203.
16. Rodríguez-Jorge F, Fernández-Velasco JI, Villarrubia N et al. Biomarkers of response to ocrelizumab in relapsing–remitting multiple sclerosis. Front Immunol. 2024; 15: 1480676.
17. Hartung HP, Benedict RHB, Berger T et al. Ocrelizumab in Early-Stage Relapsing-Remitting Multiple Sclerosis. Neurology. 2024; 103(12): e210049.
18. Seiberl M, Feige J, Hilpold P et al. Serum Neurofilament Light Chain as Biomarker for Cladribine-Treated Multiple Sclerosis Patients in a Real-World Setting. Int J Mol Sci. 2023; 24(4): 4067.
19. Voskuhl R, Kuhle J, Siddarth P et al. Decreased neurofilament light chain levels in estriol-treated multiple sclerosis. Ann Clin Transl Neurol. 2022; 9(8): 1316-20.
20. Karikari TK, Benedet AL, Ashton NJ et al. Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative. Mol Psychiatry. 2021; 26(2): 429-42.
21. Liu S, Huang Z, Zhang L et al. Plasma Neurofilament Light Chain May Be a Biomarker for the Inverse Association Between Cancers and Neurodegenerative Diseases. Front Aging Neurosci. 2020; 12: 10.
22. Andersson E, Janelidze S, Lampinen B et al. Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer’s disease. Neurobiol Aging. 2020; 95: 143-53.
23. Barker W, Quinonez C, Greig MT et al. Utility of Plasma Neurofilament Light in the 1Florida Alzheimer’s Disease Research Center (ADRC). J Alzheimers Dis. 2021; 79(1): 59-70.
24. Frank B, Ally M, Brekke B et al. Plasma p-tau 181 shows stronger network association to Alzheimer’s disease dementia than neurofilament light and total tau. Alzheimer’s & Dementia. 2022; 18(8): 1523-36.
25. Raket LL, Kühnel L, Schmidt E et al. Utility of plasma neurofilament light and total tau for clinical trials in Alzheimer’s disease. Alzheimers Dement (Amst). 2020; 12(1): e12099.
26. Buhmann C, Magnus T, Choe C. Blood neurofilament light chain in Parkinson’s disease. J Neural Transm. 2023; 130(6): 755-62.
27. Oosterveld LP, Verberk IMW, Majbour NK et al. CSF or Serum Neurofilament Light Added to α-Synuclein Panel Discriminates Parkinson’s From Controls. Mov Disord. 2020; 35(2): 288-95.
28. Aamodt WW, Waligorska T, Shen J et al. Neurofilament Light Chain as a Biomarker for Cognitive Decline in Parkinson Disease. Mov Disord. 2021; 36(12): 2945-50.
29. Lin CH, Li CH, Yang KC et al. Blood NfL: A biomarker for disease severity and progression in Parkinson disease. Neurology. 2019; 93(11): e1104-e1111.
30. Ma LZ, Zhang C, Wang H et al. Serum Neurofilament Dynamics Predicts Cognitive Progression in de novo Parkinson’s Disease. J Parkinsons Dis. 2021; 11(3): 1117-27.
31. Buhmann C, Lezius S, Pötter-Nerger M et al. Age-Adjusted Serum Neurofilament Predicts Cognitive Decline in Parkinson’s Disease (MARK-PD). Mov Disord. 2022; 37(2): 435-6.
32. Niemann L, Lezius S, Maceski A et al. Serum neurofilament is associated with motor function, cognitive decline and subclinical cardiac damage in advanced Parkinson’s disease (MARK-PD). Parkinsonism Relat Disord. 2021; 90: 44-8.
33. Sun Q, Zhao X, Li S et al. CSF Neurofilament Light Chain Elevation Predicts ALS Severity and Progression. Front Neurol. 2020; 11: 919.
34. Meyer T, Schumann P, Weydt P et al. Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: Treatment experience in clinical practice. Muscle Nerve. 2023; 67(6): 515-21.
35. Xu C, Yi T, Qing T et al. Serum neurofilament light chain: a predictive marker for outcomes following mild-to-moderate ischemic stroke. Front Neurol. 2024; 15: 1398826.
36. Gendron TF, Badi MK, Heckman MG et al. Plasma neurofilament light predicts mortality in patients with stroke. Sci Transl Med. 2020; 12(569): eaay1913.
37. Vollmuth C, Fiessler C, Montellano FA et al. Incremental value of serum neurofilament light chain and glial fibrillary acidic protein as blood-based biomarkers for predicting functional outcome in severe acute ischemic stroke. Eur Stroke J. 2024; 9(3): 751-62.
38. Zhou Z, Zeng J, Yu S et al. Neurofilament light chain and S100B serum levels are associated with disease severity and outcome in patients with aneurysmal subarachnoid hemorrhage. Front Neurol. 2022; 13: 956043.
2. Coppens S, Lehmann S, Hopley C et al. Neurofilament-Light, a Promising Biomarker: Analytical, Metrological and Clinical Challenges. Int J Mol Sci. 2023; 24(14): 11624.
3. Jung Y, Damoiseaux JS. The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer’s disease. Brain. 2024; 147(1): 12-25.
4. Shahim P, Norato G, Sinaii N et al. Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. Genes (Basel). 2024; 15(4): 496.
5. Li Y, Li F, Liu X et al. Association between serum neurofilament light chain levels and sleep disorders in patients with Parkinson’s disease. Neurosci Lett. 2023; 812: 137394.
6. Fan Z, Liu X, Liu J et al. Neurofilament Light Chain as a Potential Biomarker in Plasma for Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review and a Meta-Analysis. J Integr Neurosci. 2023; 22(4): 85.
7. Booth RA, Beriault D, Schneider R et al. Validation and generation of age-specific reference intervals for a new blood neurofilament light chain assay. Clinica Chimica Acta. 2025; 577: 120447.
8. Bar-Or A, Thanei GA, Harp C et al. Blood neurofilament light levels predict non-relapsing progression following anti-CD20 therapy in relapsing and primary progressive multiple sclerosis: findings from the ocrelizumab randomised, double-blind phase 3 clinical trials. EBioMedicine. 2023; 93: 104662.
9. Illán-Gala I, Lleo A, Karydas A et al. Plasma Tau and Neurofilament Light in Frontotemporal Lobar Degeneration and Alzheimer Disease. Neurology. 2021; 96(5): e671-83.
10. Tony AA, Kholef EFM, Elgendy DB et al. Neurofilament Light Chain Correlates with Stroke Severity and Clinical Outcome in Acute Cerebrovascular Stroke Patients. Cell Mol Neurobiol. 2025; 45(1): 39.
11. Szilasiova J, Mikula P, Rosenberger J et al. Associations between neurofilament light chain levels, disease activity and brain atrophy in progressive multiple sclerosis. Biomedical Papers. 2022; 166(3): 304-11.
12. Abdelhak A, Benkert P, Schaedelin S et al. Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis. JAMA Neurol. 2023; 80(12): 1317.
13. Kuhle J, Daizadeh N, Benkert P et al. Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing–remitting MS. Mult Scler. 2022; 28(4): 573-82.
14. Brune S, Høgestøl EA, de Rodez Benavent SA et al. Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis. Mult Scler. 2022; 28(12): 1859-70.
15. Liu N, Sun M, Zhang W et al. Prognostic value of neurofilament light chain in natalizumab therapy for different phases of multiple sclerosis: A systematic review and meta-analysis. J Clin Neurosci. 2022; 101: 198-203.
16. Rodríguez-Jorge F, Fernández-Velasco JI, Villarrubia N et al. Biomarkers of response to ocrelizumab in relapsing–remitting multiple sclerosis. Front Immunol. 2024; 15: 1480676.
17. Hartung HP, Benedict RHB, Berger T et al. Ocrelizumab in Early-Stage Relapsing-Remitting Multiple Sclerosis. Neurology. 2024; 103(12): e210049.
18. Seiberl M, Feige J, Hilpold P et al. Serum Neurofilament Light Chain as Biomarker for Cladribine-Treated Multiple Sclerosis Patients in a Real-World Setting. Int J Mol Sci. 2023; 24(4): 4067.
19. Voskuhl R, Kuhle J, Siddarth P et al. Decreased neurofilament light chain levels in estriol-treated multiple sclerosis. Ann Clin Transl Neurol. 2022; 9(8): 1316-20.
20. Karikari TK, Benedet AL, Ashton NJ et al. Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative. Mol Psychiatry. 2021; 26(2): 429-42.
21. Liu S, Huang Z, Zhang L et al. Plasma Neurofilament Light Chain May Be a Biomarker for the Inverse Association Between Cancers and Neurodegenerative Diseases. Front Aging Neurosci. 2020; 12: 10.
22. Andersson E, Janelidze S, Lampinen B et al. Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer’s disease. Neurobiol Aging. 2020; 95: 143-53.
23. Barker W, Quinonez C, Greig MT et al. Utility of Plasma Neurofilament Light in the 1Florida Alzheimer’s Disease Research Center (ADRC). J Alzheimers Dis. 2021; 79(1): 59-70.
24. Frank B, Ally M, Brekke B et al. Plasma p-tau 181 shows stronger network association to Alzheimer’s disease dementia than neurofilament light and total tau. Alzheimer’s & Dementia. 2022; 18(8): 1523-36.
25. Raket LL, Kühnel L, Schmidt E et al. Utility of plasma neurofilament light and total tau for clinical trials in Alzheimer’s disease. Alzheimers Dement (Amst). 2020; 12(1): e12099.
26. Buhmann C, Magnus T, Choe C. Blood neurofilament light chain in Parkinson’s disease. J Neural Transm. 2023; 130(6): 755-62.
27. Oosterveld LP, Verberk IMW, Majbour NK et al. CSF or Serum Neurofilament Light Added to α-Synuclein Panel Discriminates Parkinson’s From Controls. Mov Disord. 2020; 35(2): 288-95.
28. Aamodt WW, Waligorska T, Shen J et al. Neurofilament Light Chain as a Biomarker for Cognitive Decline in Parkinson Disease. Mov Disord. 2021; 36(12): 2945-50.
29. Lin CH, Li CH, Yang KC et al. Blood NfL: A biomarker for disease severity and progression in Parkinson disease. Neurology. 2019; 93(11): e1104-e1111.
30. Ma LZ, Zhang C, Wang H et al. Serum Neurofilament Dynamics Predicts Cognitive Progression in de novo Parkinson’s Disease. J Parkinsons Dis. 2021; 11(3): 1117-27.
31. Buhmann C, Lezius S, Pötter-Nerger M et al. Age-Adjusted Serum Neurofilament Predicts Cognitive Decline in Parkinson’s Disease (MARK-PD). Mov Disord. 2022; 37(2): 435-6.
32. Niemann L, Lezius S, Maceski A et al. Serum neurofilament is associated with motor function, cognitive decline and subclinical cardiac damage in advanced Parkinson’s disease (MARK-PD). Parkinsonism Relat Disord. 2021; 90: 44-8.
33. Sun Q, Zhao X, Li S et al. CSF Neurofilament Light Chain Elevation Predicts ALS Severity and Progression. Front Neurol. 2020; 11: 919.
34. Meyer T, Schumann P, Weydt P et al. Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: Treatment experience in clinical practice. Muscle Nerve. 2023; 67(6): 515-21.
35. Xu C, Yi T, Qing T et al. Serum neurofilament light chain: a predictive marker for outcomes following mild-to-moderate ischemic stroke. Front Neurol. 2024; 15: 1398826.
36. Gendron TF, Badi MK, Heckman MG et al. Plasma neurofilament light predicts mortality in patients with stroke. Sci Transl Med. 2020; 12(569): eaay1913.
37. Vollmuth C, Fiessler C, Montellano FA et al. Incremental value of serum neurofilament light chain and glial fibrillary acidic protein as blood-based biomarkers for predicting functional outcome in severe acute ischemic stroke. Eur Stroke J. 2024; 9(3): 751-62.
38. Zhou Z, Zeng J, Yu S et al. Neurofilament light chain and S100B serum levels are associated with disease severity and outcome in patients with aneurysmal subarachnoid hemorrhage. Front Neurol. 2022; 13: 956043.