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Neurofilament Light
Also known as NfL, Neurofilament light chain
Definition
Neurofilament light chain (NfL) is a neuronal cytoplasmic protein highly expressed in large-calibre myelinated axons. [1] Neurofilament proteins have been validated as specific body-fluid biomarkers of neuro-axonal injury. [2] Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders, and neurofilament levels indicate neuroaxonal injury independent of causal pathways. [3]
How it works
NfL levels increase in cerebrospinal fluid and blood proportionally to the degree of axonal damage in a variety of neurological disorders, including inflammatory, neurodegenerative, traumatic and cerebrovascular diseases. [1] Because their levels rise upon neuroaxonal damage in both cerebrospinal fluid and blood, neurofilaments indicate neuroaxonal injury independent of the specific causal pathway. [3]
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How it's measured
First- and second-generation neurofilament assays had limited sensitivity, whereas third-generation electrochemiluminescence and particularly fourth-generation single-molecule-array assays enable reliable measurement of neurofilaments throughout the range of concentrations found in blood. [3] Serum NfL has advantages over traditional measures of disease progression because it is relatively noninvasive, inexpensive and can be repeated frequently to monitor activity and treatment efficacy. [4] Further work is needed to resolve issues around comparisons across testing platforms and normalisation of reference ranges to guide interpretation of results. [4]
What levels mean
Elevated NfL reflects neurodegeneration and can potentially be used to detect the effects of disease-modifying therapies, though it is not Alzheimer's-disease-specific. [5] Interpretation of NfL is confounded by age, body mass index and blood volume, and there is considerable overlap in the range of serum NfL levels compared with healthy controls. [6]
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- 1.Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry · 2019
- 2.Khalil M, Teunissen CE, Lehmann S, Otto M, Piehl F, Ziemssen T, Bittner S, Sormani MP. Neurofilaments as biomarkers in neurological disorders - towards clinical application. Nat Rev Neurol · 2024
- 3.Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol · 2018
- 4.Freedman MS, Gnanapavan S, Booth RA, Calabresi PA, Khalil M, Kuhle J, Lycke J, Olsson T. Guidance for use of neurofilament light chain as a cerebrospinal fluid and blood biomarker in multiple sclerosis management. EBioMedicine · 2024
- 5.Leuzy A, Mattsson-Carlgren N, Palmqvist S, Janelidze S, Dage JL, Hansson O. Blood-based biomarkers for Alzheimer's disease. EMBO Mol Med · 2022
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