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Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis
Open accessAbstract
OBJECTIVE: To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS). METHODS: Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale-Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan-Meier analysis. RESULTS: CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels (r = 0.78, p < 0.0001). Blood NfL levels were approximately 4 times as high in patients with ALS compared with controls in both cohorts, and maintained a relatively constant expression during follow-up. Blood NfL levels at recruitment were strong, independent predictors of survival. The highest tertile of blood NfL at baseline had a mortality hazard ratio of 3.91 (95% confidence interval 1.98-7.94, p < 0.001). CONCLUSION: Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials. CLASSIFICATION OF EVIDENCE: This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls.
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“Due to differences in sample type (serum or plasma), results were stratified per cohort, which lead to a reduction of statistical power, while ideally one would convert concentrations between serum and plasma and use them combined.”
From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [13]
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“Lu et al. (13) combined serum and plasma NfL by using cohort-specific tertile cut-off levels in Cox regression analysis of survival.”
From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [13]
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“There are alternatives to internal standardization when using NfL from different biological matrices as independent variable.”
From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [13]
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Self-citationNeurofilament phosphoforms: Surrogate markers for axonal injury, degeneration and loss
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Neurofilament light chain as a biomarker in neurological disorders
Gaetani, L., Blennow, K., Calabresi, P., Di Filippo, M., Parnetti, L., & Zetterberg, H. (2019) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2018-320106 · Cited by 1,334
Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis
Disanto, G., Barro, C., Benkert, P., Naegelin, Y., Schädelin, S., Giardiello, A., Zecca, C., Blennow, K., Zetterberg, H., Leppert, D., et al. (2017) · Annals of Neurology · doi:10.1002/ana.24954 · Cited by 1,164
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Self-citationTrial of Antisense Oligonucleotide Tofersen for SOD1 ALS
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Bridel, C., van Wieringen, W. N., Zetterberg, H., Tijms, B. M., Teunissen, C. E., and the NFL Group, Alvarez-Cermeño, J. C., Andreasson, U., Axelsson, M., Bäckström, D. C., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.1534 · Cited by 764
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Metadata
- Authors
- Lu, C.-H., Macdonald-Wallis, C., Gray, E., Pearce, N., Petzold, A., Norgren, N., Giovannoni, G., Fratta, P., Sidle, K., Fish, M., Orrell, R., Howard, R., Talbot, K., Greensmith, L., Kuhle, J., Turner, M. R., & Malaspina, A.
- Affiliations
- Queen Mary University of London (GB)
- From the Centre for Neuroscience & Trauma (C.-H.L., G.G., J.K., A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Sobell Department of Motor Neuroscience and Movement Disorders (C.-H.L., L.G.), Departments of Neuroinflammation (A.P.), Neurodegenerative Disease (P.F.), Molecular Neuroscience (K.S.), and Clinical Neuroscience (R.O.), and MRC Centre for Neuromuscular Diseases (R.O., L.G.), UCL Institute of Neurology, London; MRC...
- Corresponding author
- Turner, Martin R.
- Malaspina, Andrea
- ORCID
- Venue
- Neurology
- Published
- 2015-06-02
- Volume
- 84
- Issue
- 22
- Pages
- 2247-2257
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC4456658
- OpenAlex
- W2136911505
- Cited by
- 563
- References
- 2
- Citations by year
- 2026: 42 · 2025: 60 · 2024: 58 · 2023: 44 · 2022: 56 · 2021: 64 · 2020: 65 · 2019: 56 · 2018: 47 · 2017: 33 · 2016: 24 · 2015: 13
- FWCI
- 27.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- Funders
- Motor Neurone Disease Association (Malaspina/Apr13/6097, MALASPINA/APR08/RF/6039, TURNER/JAN13/944-795, FRATTA/JAN15/946-795)
- Research Councils UK
- Medical Research Council (MR/J011932/1, MR/K01014X/1, MR/K000780/1, MR/M008606/1, MR/K000608/1)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- neurofilament light chain, amyotrophic lateral sclerosis, sporadic ALS, cerebrospinal fluid biomarkers, serum biomarkers, plasma biomarkers, prognostic factors, disease progression, survival prediction, electrochemiluminescence immunoassay, pharmacodynamic biomarkers
- MeSH terms
- Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Prognosis, Cohort Studies, Biomarkers, Neurofilament Proteins, Disease Progression
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