Neurofilaments as biomarkers in neurological disorders
Open accessAbstract
Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. Reliable quantification and longitudinal follow-up of such damage are important for assessing disease activity, monitoring treatment responses, facilitating treatment development and determining prognosis. The neurofilament proteins have promise in this context because their levels rise upon neuroaxonal damage not only in the cerebrospinal fluid (CSF) but also in blood, and they indicate neuroaxonal injury independent of causal pathways. First-generation (immunoblot) and second-generation (enzyme-linked immunosorbent assay) neurofilament assays had limited sensitivity. Third-generation (electrochemiluminescence) and particularly fourth-generation (single-molecule array) assays enable the reliable measurement of neurofilaments throughout the range of concentrations found in blood samples. This technological advancement has paved the way to investigate neurofilaments in a range of neurological disorders. Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease. We also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice.
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NfL is a structural protein that can be detected in the blood at elevated levels in a variety of neurological diseases.
“NfL is a structural protein that can be detected in the blood at elevated levels in a variety of neurological diseases (2–5).”
From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [3]
Elevated NfL levels in the CSF implicate neuronal damage.
“It is also well established that elevated NfL levels in the CSF implicate a neuronal damage.34”
From Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia (2020) · cites this paper as [34]
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- Authors
- Khalil, M., Teunissen, C. E., Otto, M., Piehl, F., Sormani, M. P., Gattringer, T., Barro, C., Kappos, L., Comabella, M., Fazekas, F., Petzold, A., Blennow, K., Zetterberg, H., & Kuhle, J.
- Affiliations
- Medical University of Graz (AT)
- Amsterdam Neuroscience (NL)
- University Hospital Ulm (DE)
- Karolinska Institutet (SE)
- Ospedale Policlinico San Martino (IT)
- University of Basel (CH)
- Universitat Autònoma de Barcelona (ES)
- Moorfields Eye Hospital NHS Foundation Trust (GB)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Khalil, Michael
- ORCID
- Venue
- Nature Reviews Neurology
- Published
- 2018-08-31
- Volume
- 14
- Issue
- 10
- Pages
- 577-589
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W2889223700
- Cited by
- 1,988
- References
- 13
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- 21.77
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- journal article
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- en
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- Funders
- National Science Foundation
- ALS Association
- Torsten Söderbergs Stiftelse
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (160221)
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neurofilaments, neurofilament light chain, neuroaxonal damage, cerebrospinal fluid biomarkers, blood-based biomarkers, single molecule array, electrochemiluminescence immunoassay, multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, disease activity monitoring
- MeSH terms
- Brain Injuries, Traumatic, Aging, Amyotrophic Lateral Sclerosis, Bipolar Disorder, Dementia, Humans, Huntington Disease, Immunoassay, Multiple Sclerosis, Parkinson Disease, Biomarkers, Neurofilament Proteins, Stroke
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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