Indication

Suspected neuronal damage in the CNS or PNS

Method

SIMOA (single molecule array)
Can be tested in serum, EDTA-plasma or CSF.

Response

The result is reported as ng/L. If urgent NfL-testing is required, please contact the laboratory at +46 40 53 76 60.

Reference interval (serum/EDTA-plasma):

Age	Concentration
18-40 years:	2.8 – 9.7 ng/L
41-65 years:	4.6 – 21.4 ng/L
>65 years:	7.5 – 53.8 ng/L

Reference interval (CSF):

Age	Concentration
<30 years:	<380 ng/L
30-39 years:	<560 ng/L
40-59 years:	<890 ng/L
≥60 years:	<1850 ng/L

There are several benefits of measuring NfL in serum/plasma rather than in CSF:

more comfortable sampling for the patient and less time needed for healthcare professionals.
blood sampling can be performed in conjunction with routine blood sampling and can even be performed in primary care.
samples can be taken more often, which is an advantage if closer monitoring is needed.

Interpretation

Neurofilament light chain protein (NfL, about 68 kDa) is one of many proteins in the neuronal cytoskeleton, the protein is released upon axonal damage in the central nervous system (CNS) and can be detected in the cerebrospinal fluid (CSF) and after passage over the blood brain barrier also in serum and EDTA-plasma. Serum/plasma NfL levels are several times lower than in CSF, but the correlation is high. Plasma levels are somehow lower than in serum (approx. 10% lower). The level of NfL in serum/plasma can thus be used as a marker of neuronal degeneration in the CNS. Elevated levels of NfL are however an unspecific marker of neuronal degeneration and do not tell about the underlying cause.

The level of NfL in CSF positively correlates to the degree of tissue damage and is associated with disability scores in several neurodegenerative diseases (Alzheimer’s disease, Multiple Sclerosis (MS), dementia, amyotrophic lateral sclerosis (ALS) and spinal cord injury etc.). In Multiple Sclerosis increased levels are found in inflammatory active disease and can be used to monitor response to disease modifying treatments. Hence, the clinical value of being able to follow therapy response, relapses, and disease progression with following the NfL levels, are high in blood-based and CSF measurements.

Significantly elevated levels are seen in widespread axonal injury, e.g., in encephalitis. High levels can also be seen in ALS with upper motor neuron damage. The level of NfL is of great value in monitoring the course of the disease in demyelinating diseases. Since the NfL level varies greatly between individuals in the normal population, the reference ranges are wide. We therefore recommend that patients are monitored individually and that a sample is taken at a calm stage when the disease is well controlled, i.e., without signs of active inflammation during the three immediately preceding months. That value can then be used as the individual´s own reference and when more than 20% difference is seen between two samples the difference is judged to be significant.

In dementia, mildly elevated CSF levels are usually seen with slightly higher levels in frontotemporal and vascular dementia compared to Alzheimer's disease. However, the experience of serum/plasma NfL in these disease groups is limited

References

Disanto, G. et al., Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Annals of neurology 2017, 81(6), 857–870.
Schott JM, et al., Stability of blood-based biomarkers of Alzheimer's disease over multiple freeze-thaw cycles. Alzheimer’s Dement (Amst). 2018 Jul 2; 10:448-451.
Jens Kuhle et al., Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology. 2019 Mar 5;92(10)
Hviid CVB et al., Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults. Scand J Clin Lab Invest. 2020 Feb 20:1-5.
Khalil M et al., Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat Commun. 2020 Feb 10;11(1):812.
Mattsson N et al. Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurol. 2017 May 1;74(5):557-566.
Piehl F et al. Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod. Mult Scler. 2018 Jul;24(8):1046-1054.
Lewczuk P et al. Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther. 2018; 10: 71.
Bacioglu M et al. Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases. Neuron. 2016 Jul 20;91(2):494-496.

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