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.

Result

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

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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Neurology

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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 serum, EDTA-plasma eller likvor (Csv).

Resultat

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 (Csf):


  • 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 neuronalt cytoskelett i både centrala och perifera nervsystemet (CNS och PNS). Vid axonala skador i CNS läcker NfL ut i likvor, förhöjda nivåer kan detekteras i serum/plasma. Vid skador i CNS är nivån i blod betydligt lägre än i likvor, men korrelationen är hög. NfL i serum/plasma kan spegla graden av neuronsönderfall vid skador i såväl CNS som PNS. Analys i plasma ger ca 10% lägre nivåer än i serum.

Förhöjda nivåer av NfL är en ospecifik markör för neuronalt sönderfall och säger inte något om bakomliggande orsak. Nivån av NfL i blod kan även vara av värde för monitorering av neuronal skada. Kraftigt förhöjda nivåer i likvor talar för utbredd diffus axonal skada och kan ses vid flera olika tillstånd, t.ex. encefalit. Höga nivåer kan även ses vid ALS med övre motorneuronskada.

Eftersom nivån av NfL i serum/plasma varierar mycket mellan olika individer i normalpopulationen är referensintervallen breda. Det är därför lämpligt att patienter följs individuellt och att ett prov tas när sjukdomen inte har visat några tecken till aktiv inflammation under de tre närmast föregående månaderna. Det värdet kan sedan användas som individens egen referens och >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 begränsad.

Vid oklar orsak till skada i CNS undersöks lämpligen NfL tillsammans med andra hjärnskademarkörer i likvor; GFAp (astrocytskademarkör), Tau (cortikal skademarkör), Beta-amyloid (demensmarkör), och S-100 (akut hjärnskada). Dessutom kan analys av neuronspecifikt enolas (NSE) i serum vara av värde vid akut hjärnskada och är även markör för vissa neuroendokrina tumörer.

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.

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