Vial

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 oftenwhich 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

  1. Disanto, G. et al., Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Annals of neurology 2017, 81(6), 857–870.
  2. 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.
  3. Jens Kuhle et al., Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology. 2019 Mar 5;92(10)
  4. 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.
  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.
  6. 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.
  7. 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. 
  8. Lewczuk P et al. Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther. 2018; 10: 71.
  9. 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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Vial

ENSKILD ANALYS 994

Neurofilament light (NfL)

Indikation

Misstänkt neuronskada i CNS eller PNS

Metod

SIMOA (single molecule array)
Analys kan utföras i serumEDTA-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 rikligt i myeliniserade axon. Vid axonala skador i CNS läcker NfL ut i likvor och förhöjda nivåer kan även detekteras i serum/plasma. Nivåerna i serum/plasma är flerfaldigt lägre än i likvor men korrelationen är hög, men analys i plasma ger 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 dock en ospecifik markör för neuronalt sönderfall och säger inte något om bakomliggande orsak.

Kraftigt förhöjda nivåer ses vid utbredd axonal skada, t.ex. vid encefalit. Höga nivåer kan även ses vid ALS med övre motorneuronskada. Nivån av NfL har stort värde vid monitorering av sjukdomsförloppet vid demyeliniserande sjukdomar. Eftersom nivån av Nfl varierar mycket mellan olika individer i normalpopulationen är referensintervallen dock breda. Vi rekommenderar därför att patienter följs individuellt och att ett prov tas i lugnt skede när sjukdomen är välkontrollerad dvs utan tecken till aktiv inflammation under de tre närmast föregående månaderna. Det värdet kan sedan användas som individens egen referens och vid mer än 20% skillnad mellan två prover bedöms vara signifikant.

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/plasma på dessa sjukdomsgrupper är dock begränsad.

 

Referenser

  1. Disanto, G. et al., Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Annals of neurology 2017, 81(6), 857–870.
  2. 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.
  3. Jens Kuhle et al., Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology. 2019 Mar 5;92(10)
  4. 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.
  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.
  6. 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.  
  7. 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. 
  8. Lewczuk P et al. Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther. 2018; 10: 71. 
  9. 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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