Neurofilament light chain as a biomarker in neurological disorders
Open accessAbstract
In the management of neurological diseases, the identification and quantification of axonal damage could allow for the improvement of diagnostic accuracy and prognostic assessment. Neurofilament light chain (NfL) is a neuronal cytoplasmic protein highly expressed in large calibre myelinated axons. Its levels increase in cerebrospinal fluid (CSF) and blood proportionally to the degree of axonal damage in a variety of neurological disorders, including inflammatory, neurodegenerative, traumatic and cerebrovascular diseases. New immunoassays able to detect biomarkers at ultralow levels have allowed for the measurement of NfL in blood, thus making it possible to easily and repeatedly measure NfL for monitoring diseases’ courses. Evidence that both CSF and blood NfL may serve as diagnostic, prognostic and monitoring biomarkers in neurological diseases is progressively increasing, and NfL is one of the most promising biomarkers to be used in clinical and research setting in the next future. Here we review the most important results on CSF and blood NfL and we discuss its potential applications and future directions.
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Proteins with associations in APOE region featured known AD biomarkers, including four members of the 14-3-3 protein family and neurofilament light and heavy chains.
“Proteins with associations in this region featured known AD biomarkers, including four members of the 14-3-3 protein family and neurofilament light and heavy chains37,38.”
From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [38]
The section on NfL in the diagnostic work-up of Alzheimer’s disease reports elevated neurofilament light in AD patients and discusses its potential as a biomarker. It does not establish neurofilament heavy chain as an AD biomarker; its discussion of heavy chain concerns ALS. The APOE-region associations are the citing authors’ findings, not a finding attributed to this review. (LLM, conf=0.86)
Experimental — accuracy not yet measuredNfL is a reliable biomarker of neuroaxonal damage and is used for diagnosis, prognosis, and monitoring of treatment response in several neurodegenerative conditions.
“NfL is a reliable biomarker of neuroaxonal damage and is used for the diagnosis (although limited due to its nondisease specificity), prognosis, and monitoring of treatment response in several neurodegenerative conditions [38].”
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- References for this Review were identified by searches of PubMed between 1990 and January 31 st 2019, and references from relevant articles. The following search terms were used: "neurofilament light", "neurofilament light chain", "neurofilament light protein", "NfL"; "cerebrospinal fluid", "CSF", "serum", "plasma", "blood"; "demyelinating diseases", "multiple sclerosis", "MS", "clinically isolated syndrome", "CIS", "radiologically isolated syndrome", "RIS", "optic neuritis", "myelitis"; "amyotrophic lateral sclerosis", "ALS", "motor neuron diseases"; "frontotemporal dementia", "frontotemporal lobar degeneration", "FTD", "FTLD", "primary progressive aphasia", "PPA", "Alzheimer's disease", "AD", "mild cognitive impairment", "MCI", "dementia", "Parkinson's disease", "PD", "Parkinson's disease dementia", "PDD", "dementia with Lewy body", "DLB", "progressive supranuclear palsy", "PSP", "multiple system atrophy", "MSA", "corticobasal syndrome", "CBS", "Huntington's disease", "HD", "normal pressure hydrocephalus", "NPH", "HIV", "AIDS", "AIDS dementia complex", "ADC", "antiretroviral therapy", "ART", "Stroke", "transient ischemic attack", "hemorrhage", "subarachnoid hemorrhage", "SAH", "intracerebral hemorrhage", "cardiac arrest", "resuscitation", "autoimmune encephalitis", "paraneoplastic encephalitis". There were no language restrictions. The final reference list was generated based on relevance to the topics covered in this Review. Additional references can be found in the online supplementary file.
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- Authors
- Gaetani, L., Blennow, K., Calabresi, P., Di Filippo, M., Parnetti, L., & Zetterberg, H.
- Affiliations
- University of Perugia (IT)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Gaetani, Lorenzo
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2019-04-09
- Volume
- 90
- Issue
- 8
- Pages
- 870-881
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- OpenAlex
- W2939789416
- Cited by
- 1,334
- References
- 63
- Citations by year
- 2026: 207 · 2025: 250 · 2024: 247 · 2023: 222 · 2022: 168 · 2021: 130 · 2020: 88 · 2019: 20
- FWCI
- 13.55
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- neurofilament light chain, axonal injury, cerebrospinal fluid biomarkers, blood biomarkers, neurodegenerative diseases, traumatic brain injury, cerebrovascular disease, disease surveillance, prognostic factors, diagnostic biomarkers
- MeSH terms
- Humans, Nervous System Diseases, Prognosis, Biomarkers, Neurofilament Proteins
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