INDIVIDUAL TEST 994
Neurofilament light (NfL)
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 protein (NfL, about 68 kD) is a subunit of neurofilament that is an important cytoskeleton in the neuron and is most abundant in myelinated axons. In axonal damage, NfL leaks into CSF and the level reflects the degree of neuronal degeneration. Elevated NfL levels can also be detected in the serum/plasma. Serum/plasma 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 a nonspecific marker of neuronal degeneration and do not tell about the underlying cause. Significantly elevated levels indicate widespread diffuse axonal injury and can be seen at e.g. encephalitis. High levels can also be seen in ALS with upper motor neuron damage. In multiple sclerosis (MS), elevated NfL levels are usually seen with ongoing neuroinflammation and the level of NfL can be followed to monitor the effect of immunomodulatory therapy.
The level of NfL is of great value in monitoring the course of the disease in demyelinating diseases and is included in the follow-up routine of relapsing multiple sclerosis. 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 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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ENSKILD ANALYS 994
Neurofilament light (NfL)
Indikation
Misstänkt neuronskada i CNS eller PNS
Metod
SIMOA (single molecule array)
Analys kan utföras i serum, EDTA-plasma eller likvor (Csv).
Svar
Resultat rapporteras som ng/L. Vid behov av akut NfL-analys, kontakta laboratoriet på 040- 53 76 60.
Referensintervall (serum/EDTA-plasma):
|
Ålder |
Koncentration |
|
18-40 år: |
2.8 – 9.7 ng/L |
|
41-65 år: |
4.6 – 21.4 ng/L |
|
>65 år: |
7.5 – 53.8 ng/L |
Referensintervall (CSF/likvor):
|
Ålder |
Koncentration |
|
<30 år: |
<380 ng/L |
|
30-39 år: |
<560 ng/L |
|
40-59 år: |
<890 ng/L |
|
≥60 år: |
<1850 ng/L |
Det finns flera fördelar med att mäta NfL i serum/plasma i stället för i likvor (Csv):
- mindre obehag vid provtagning för patienten och mindre tidsåtgång för sjukvårdspersonal.
- blodprovstagning kan utföras i samband med rutinblodprovstagning och även ske i primärvården.
- Provet kan tas oftare vilket är en fördel vid behov av tätare monitorering.
Tolkning
Neurofilament light protein (NfL, ca 68 kD) utgör en subenhet i neurofilament som är ett viktigt cytoskelett i neuron och förekommer rikligast i myeliniserade axon. Vid axonala skador läcker NfL ut i likvor och nivån avspeglar graden av neuronsönderfall. NfL förhöjda nivåer kan även detekteras i serum/plasma. Nivåerna i serum/plasma är flerfaldigt lägre än i likvor men korrelationen är hög, dock ger analys i plasma något lägre nivåer än serum (ca 10% lägre). Nivån av NfL i serum/plasma kan därmed användas som markör för neuronsönderfall i CNS.
Förhöjda nivåer av NfL är en ospecifik markör för neuronalt sönderfall och säger inte något om bakomliggande orsak. Kraftigt förhöjda nivåer talar för utbredd diffus axonal skada och kan ses vid t.ex. encefalit. Höga nivåer kan även ses vid ALS med övre motorneuronskada. Vid multipel skleros (MS) ses vanligtvis förhöjda nivåer vid pågående neuroinflammation och nivån av NfL kan följas för att monitorera effekt av immunmodulerande behandling.
Nivån av NfL har stort värde vid monitorering av sjukdomsförloppet vid demyeliniserande sjukdomar och ingår vid rutinuppföljning av skovvis multipel skleros. Vid demenssjukdomar ses oftast lätt-måttligt förhöjda nivåer i likvor med något högre nivåer vid frontotemporal och vaskulär demens jämfört med Alzheimers sjukdom. Erfarenheten av NfL i serum på dessa sjukdomsgrupper är dock begränsad.
Referenser
- 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.