Indication

Suspicion of neuronal damage in the CNS or PNS

Sample material

Serum

Minim. volume: 0,5 mL

CSF

Minim. volume: 0,5 mL

EDTA-plasma

Minim. volume: 0,5 mL

Transport

Serum

Within Sweden: room temperature
International: room temperature

CSF

Within Sweden: room temperature
International: room temperature

EDTA plasma

Within Sweden: room temperature/frozen (stable for 48h in room temperature)
International: room temperature/frozen (stable for 48h in room temperature)

Method

Single Molecule Array (SIMOA)

Reference interval

Serum/EDTA plasma

Age	Reference interval
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

CSF

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

Result

Results are reported as a concentration in ng/L.

Interpretation

Neurofilaments are parts of the cytoskeletal structure of neurons and are abundantly found in axons. They are important for maintaining size and providing structural support for the neuron. There are currently five known neurofilament proteins that can co-assemble in different combinations. Neurofilament light (NfL) is the most commonly used biomarker.

During axonal damage in the CNS, NfL leaks into CSF and can often also be detected in serum and plasma. Levels of NfL in serum and plasma are several times lower than in CSF, but the correlation is high – and they can be used as a marker of neuronal damage in both CNS and PNS. Analysis in plasma results in approximately 10% lower NfL levels than in serum.

NfL is a general marker of neuronal damage – it does not say anything about the underlying cause. Significantly elevated levels indicate widespread diffuse axonal damage and can be seen in several conditions, including encephalitis. High levels can also be seen in ALS with upper motor neuron damage.

NfL levels in blood can also be used for monitoring neuronal damage. Since the level of NfL varies between individuals and increases with age, the reference intervals are wide and age-related. We therefore recommend that a sample is taken when the disease is well controlled – with no signs of active inflammation in the last three months. This baseline value can be used as the individual's own reference, with a difference of >20% between samples being defined 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, there is limited data on NfL in serum and plasma in these groups.

In case of unclear cause of injury in the CNS, NfL is investigated together with other brain injury markers in CSF: GFAp (astrocyte injury marker), Tau (cortical injury marker), Beta-amyloid (dementia marker), and S-100 (acute brain injury). In addition, analysis of neuron-specific enolase (NSE) in serum may be of value in acute brain injury and is also a marker for some neuroendocrine tumors.

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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