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Neurofilament Light Chain (NfL), Plasma

This test is used to assess for neuronal injury or neurodegeneration in individuals being evaluated or monitored for neurologic conditions.

Test Summary

Neurofilament Light Chain (NfL), Plasma

Test code: 13979

Clinical use

Assess for neuronal injury or neurodegeneration
Assess prognosis and monitor treatment response in multiple sclerosis
Assess disease progression in multiple sclerosis and Alzheimer's disease (AD)

Clinical background

Neurofilament light chain (NfL) is a structural protein expressed exclusively in neurons. Upon neuronal degeneration or injury, NfL is released into extracellular space, resulting in increased concentrations in cerebrospinal fluid (CSF) and peripheral blood.1 Though NfL levels are lower in blood than in CSF, advancements in assay development have enabled the use of blood-based NfL as a more accessible biomarker of neuronal injury and/or neurodegeneration.1 Blood-based NfL levels are elevated in many neurodegenerative diseases, such as multiple sclerosis, AD, frontotemporal dementia, amyotrophic lateral sclerosis (ALS), and parkinsonian syndromes, as well as traumatic brain- or cerebral vascular-induced injury and peripheral neuropathies.1–5

NfL is generally useful for informing prognosis and monitoring disease progression.1 Its use is most well-established in multiple sclerosis. The Consortium of Multiple Sclerosis Centers recommends baseline and regular follow-up assessment of NfL for obtaining prognostic information and evaluating treatment response.3 Elevated baseline or increasing NfL levels can predict multiple sclerosis relapses and other disease activity.6 NfL is also a biomarker of neurodegeneration in AD. As elevated levels are associated with AD progression, NfL has emerged as a candidate biomarker in the biological definition of AD.7,8

NfL is also useful in neural injury assessment. Patients with mild traumatic brain injury (ie, concussion), particularly when related to sports activity, have higher NfL levels than uninjured individuals.4 NfL levels are elevated following a stroke or cardiac arrest and are associated with severity of the resulting brain injury and neurologic outcome.1 Levels are also elevated in peripheral neuropathies and are associated with poorer outcomes.1,5

Although lacking specificity for any given disease, measuring NfL can be useful for certain differential diagnoses. Levels are elevated in frontotemporal dementia vs psychiatric disorders, ALS vs motor neuron disease mimics, and atypical parkinsonian syndromes vs Parkinson disease.1,2,9–11

The Neurofilament Light Chain (NfL), Plasma test (test code 13979) provides an accessible, minimally invasive option for assessing neurodegeneration or neuronal injury. As described above, this test can provide support throughout the neurologic care pathway depending on the clinical context.

Individuals suitable for testing

Individuals being evaluated or monitored for neurologic disease or injury

Method

Electrochemiluminescence immunoassay
Reportable range: 0.54 pg/mL to 700.00 pg/mL

Interpretive information

Interpretation of plasma NfL test results depends on the clinical context. Normal plasma NfL levels are generally consistent with the absence of clinically relevant neuronal injury or neurodegeneration. In patients receiving therapy for multiple sclerosis, normal or decreased levels of NfL indicate treatment response and are associated with a more favorable prognosis.3

Elevated plasma NfL levels are consistent with clinically relevant neuronal injury or neurodegeneration. In patients with a known neurologic condition, elevated NfL or increased levels from an established, patient-specific baseline may indicate poorer prognosis and/or disease progression.1 In patients with diagnostic uncertainty, elevated NfL may support differential diagnosis of a suspected neurologic condition.1

NfL levels can be influenced by many factors, including age, body mass index, kidney disease, and a history of diabetes or cardiovascular conditions.1 The results of this assay should be considered in conjunction with the findings from medical and family history, neuroimaging, and physical, neurological, and neuropsychological examination.

References

Khalil M, Teunissen CE, Lehmann S, et al. Neurofilaments as biomarkers in neurological disorders — towards clinical application. Nat Rev Neurol. 2024;20(5):269-287. doi:10.1038/s41582-024-00955-x
Ashton NJ, Janelidze S, Khleifat AA, et al. A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. 2021;12(1):3400. doi:10.1038/s41467-021-23620-z
Freedman MS, Gnanapavan S, Booth RA, et al. Guidance for use of neurofilament light chain as a cerebrospinal fluid and blood biomarker in multiple sclerosis management. eBioMedicine. 2024;101:104970. doi:10.1016/j.ebiom.2024.104970
Karantali E, Kazis D, McKenna J, et al. Neurofilament light chain in patients with a concussion or head impacts: a systematic review and meta-analysis. Eur J Trauma Emerg Surg. 2022;48(3):1555-1567. doi:10.1007/s00068-021-01693-1
Fundaun J, Kolski M, Molina-Álvarez M, et al. Types and concentrations of blood-based biomarkers in adults with peripheral neuropathies. JAMA Netw Open. 2022;5(12):e2248593. doi:10.1001/jamanetworkopen.2022.48593
Thebault S, Reaume M, Marrie RA, et al. High or increasing serum NfL is predictive of impending multiple sclerosis relapses. Mult Scler Relat Disord. 2022;59:103535. doi:10.1016/j.msard.2022.103535
Jack CR, Bennett DA, Blennow K, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimer’s Dement. 2018;14(4):535-562. doi:10.1016/j.jalz.2018.02.018
Mattsson N, Cullen NC, Andreasson U, et al. Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2019;76(7):791-799. doi:10.1001/jamaneurol.2019.0765
Ducharme S, Dols A, Laforce R, et al. Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders. Brain. 2020;143(6):1632-1650. doi:10.1093/brain/awaa018
Feneberg E, Oeckl P, Steinacker P, et al. Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology. 2018;90(1):e22-e30. doi:10.1212/wnl.0000000000004761
Angelopoulou E, Bougea A, Papadopoulos A, et al. CSF and circulating NfL as biomarkers for the discrimination of Parkinson disease from atypical parkinsonian syndromes. Neurol Clin Pr. 2021;11(6):e867-e875. doi:10.1212/cpj.0000000000001116

Content reviewed 06/2024

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13979 - Neurofilament Light Chain (NfL)

Neurofilament light (NfL) is an intermediate filament protein found specifically in the neuronal cytoskeleton. It can be released into the extracellular space through axonal degradation, and it has been shown that varying NfL levels are an indicator of neuroaxonal damage, irrespective of the cause, and can therefore be associated with a variety of neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, or Alzheimer's disease, as well as acute situations such as traumatic brain injury and others. NfL is thus considered a promising biomarker for, e.g. disease activity, progression, prognosis, and monitoring effectiveness of therapies. As NfL can be measured in both cerebrospinal fluid (CSF) and blood, it holds great potential for routine clinical use.

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

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