Cited by 142Hereditary Neurological DisordersMultiple Sclerosis Research StudiesAmyotrophic Lateral Sclerosis Research

Neurofilament Light Chain as a Biomarker, and Correlation with Magnetic Resonance Imaging in Diagnosis of CNS-Related Disorders

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Alirezaei, Zahra, Pourhanifeh, Mohammad Hossein, Borran, Sarina, Nejati, Majid, Mirzaei, Hamed, Hamblin, Michael R.·2020·Molecular Neurobiology

Abstract

The search for diagnostic and prognostic biomarkers for neurodegenerative conditions is of high importance, since these disorders may present difficulties in differential diagnosis. Biomarkers with high sensitivity and specificity are required. Neurofilament light chain (NfL) is a unique biomarker related to axonal damage and neural cell death, which is elevated in a number of neurological disorders, and can be detected in cerebrospinal fluid (CSF), as well as blood, serum, or plasma samples. Although the NfL concentration in CSF is higher than that in blood, blood measurement may be easier in practice due to its lesser invasiveness, reproducibility, and convenience. Many studies have investigated NfL in both CSF and serum/plasma as a potential biomarker of neurodegenerative disorders. Neuroimaging biomarkers can also potentially improve detection of CNS-related disorders at an early stage. Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) are sensitive techniques to visualize neuroaxonal loss. Therefore, investigating the combination of NfL levels with indices extracted from MRI and DTI scans could potentially improve diagnosis of CNS-related disorders. This review summarizes the evidence for NfL being a reliable biomarker in the early detection and disease management in several CNS-related disorders. Moreover, we highlight the correlation between MRI and NfL and ask whether they can be combined.

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  • Systematic reviews and meta-analyses encountered limitations when combining results from studies using serum and plasma NfL concentrations.

    “Studies using serum as well as plasma NfL concentrations are abundant in the literature, but systematic reviews and meta-analyses encountered limitations when combining results from these studies (7–9).”

    From A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies (2022) · cites this paper as [7]

    The Abstract says many studies have measured NfL in serum or plasma. The “Assays to detect soluble neurofilaments” section says validation studies and meta-analyses emphasized a need to standardize assays, but it does not say that reviews had difficulty combining serum-based and plasma-based results specifically. (LLM, conf=0.79)

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  1. [35]Steinacker P, Feneberg E, Weishaupt J, Brettschneider J, Tumani H, Andersen PM, von Arnim CA, Böhm S, Kassubek J, Kubisch C (2016) Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. Journal of neurology, neurosurgery, and psychiatry 87 (1): 12– 20 26296871
  2. [59]Scherling CS, Hall T, Berisha F, Klepac K, Karydas A, Coppola G, Kramer JH, Rabinovici G, Ahlijanian M, Miller BL, Seeley W, Grinberg LT, Rosen H, Meredith J Jr., Boxer AL (2014) Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol 75 (1): 116– 126. doi: 10.1002/ana.24052 24242746 PMC4020786 · DOI · Paper page
  3. [74]Lin YS, Lee WJ, Wang SJ, Fuh JL (2018) Levels of plasma neurofilament light chain and cognitive function in patients with Alzheimer or Parkinson disease. 8 (1): 17368. doi: 10.1038/s41598-018-35766-w 30478269 PMC6255914 · DOI · Paper page
  4. [83]Soylu-Kucharz R, Sandelius A, Sjogren M, Blennow K, Wild EJ (2017) Neurofilament light protein in CSF and blood is associated with neurodegeneration and disease severity in Huntington’s disease R6/2 mice. 7 (1): 14114. doi: 10.1038/s41598-017-14179-1 PMC5658344 29074982 · DOI
  5. [96]Tortelli R, Ruggieri M, Cortese R, D’errico E, Capozzo R, Leo A, Mastrapasqua M, Zoccolella S, Leante R, Livrea P (2012) Elevated cerebrospinal fluid neurofilament light levels in patients with amyotrophic lateral sclerosis: a possible marker of disease severity and progression. European journal of neurology 19 (12): 1561– 1567. doi: 10.1111/j.1468-1331.2012.03777.x 22680408 · DOI
  6. [97]Menke RA, Gray E, Lu CH, Kuhle J, Talbot K, Malaspina A, Turner MR (2015) CSF neurofilament light chain reflects corticospinal tract degeneration in ALS. Annals of clinical and translational neurology 2 (7): 748– 755 26273687 PMC4531057
  7. [98]Lu C-H, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, Giovannoni G, Fratta P, Sidle K, Fish M (2015) Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84 (22): 2247– 2257. doi: 10.1212/WNL.0000000000001642. 25934855 PMC4456658 · DOI · Paper page
  8. [99]Gaiani A, Martinelli I, Bello L, Querin G, Puthenparampil M, Ruggero S, Toffanin E, Cagnin A, Briani C, Pegoraro E (2017) Diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis: neurofilament light chain levels in definite subtypes of disease. JAMA neurology 74 (5): 525– 532. doi: 10.1001/jamaneurol.2016.5398 28264096 PMC5822207 · DOI
  9. [100]Tortelli R, Copetti M, Ruggieri M, Cortese R, Capozzo R, Leo A, D’errico E, Mastrapasqua M, Zoccolella S, Pellegrini F (2015) Cerebrospinal fluid neurofilament light chain levels: marker of progression to generalized amyotrophic lateral sclerosis. European journal of neurology 22 (1): 215– 218. doi: 10.1111/ene.12421. 24750431 · DOI
  10. [109]Hansson O, Janelidze S, Hall S, Magdalinou N, Lees AJ, Andreasson U, Norgren N, Linder J, Forsgren L, Constantinescu R (2017) Blood-based NfL A biomarker for differential diagnosis of parkinsonian disorder. Neurology 88 (10): 930– 937. doi: 10.1212/WNL.0000000000003680. 28179466 PMC5333515 · DOI · Paper page
  11. [110]Abdo WF, Bloem BR, Van Geel WJ, Esselink RA, Verbeek MM (2007) CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson’s disease. Neurobiology of aging 28 (5): 742– 747 16678934
  12. [111]Hall S, Öhrfelt A, Constantinescu R, Andreasson U, Surova Y, Bostrom F, Nilsson C, Widner H, Decraemer H, Nägga K (2012) Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Archives of neurology 69 (11): 1445– 52 22925882
  13. [116]Kuhle J, Barro C, Disanto G, Mathias A, Soneson C, Bonnier G, Yaldizli Ö, Regeniter A, Derfuss T, Canales M (2016) Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity. Multiple Sclerosis Journal 22 (12): 1550– 1559 26754800
  14. [119]Novakova L, Zetterberg H, Sundström P, Axelsson M, Khademi M, Gunnarsson M, Malmeström C, Svenningsson A, Olsson T, Piehl F (2017) Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology 89 (22): 2230– 2237. doi: 10.1212/WNL.0000000000004683 29079686 PMC5705244 · DOI · Paper page
  15. [135]Lewczuk P, Ermann N, Andreasson U, Schultheis C, Podhorna J, Spitzer P, Maler JM, Kornhuber J, Blennow K, Zetterberg H (2018) Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimer’s research & therapy 10 (1): 71. doi: 10.1186/s13195-018-0404-9. PMC6064615 30055655 · DOI
  16. [136]Weston PS, Poole T, Ryan NS, Nair A, Liang Y, Macpherson K, Druyeh R, Malone IB, Ahsan RL, Pemberton H (2017) Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration. Neurology 89 (21): 2167– 2175. doi: 10.1212/WNL.0000000000004667. 29070659 PMC5696646 · DOI · Paper page
  17. [140]Waldö ML, Santillo AF, Passant U, Zetterberg H, Rosengren L, Nilsson C, Englund E (2013) Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia. BMC neurology 13 (1): 54. doi: 10.1186/1471-2377-13-54. 23718879 PMC3671150 · DOI · Paper page
  18. [141]Meeter LH, Dopper EG, Jiskoot LC, Sanchez-Valle R, Graff C, Benussi L, Ghidoni R, Pijnenburg YA, Borroni B, Galimberti D (2016) Neurofilament light chain: a biomarker for genetic frontotemporal dementia. Annals of clinical and translational neurology 3 (8): 623– 636. doi: 10.1002/acn3.325. 27606344 PMC4999594 · DOI · Paper page
  19. [147]De Jong D, Jansen RW, Pijnenburg YA, van Geel WJ, Borm GF, Kremer BP, Verbeek MM (2007) CSF neurofilament proteins in the differential diagnosis of dementia. Journal of Neurology, Neurosurgery & Psychiatry 78(9): 936– 8. PMC2117885 17314187
  20. [149]Weydt P, Oeckl P, Huss A, Müller K, Volk AE, Kuhle J, Knehr A, Andersen PM, Prudlo J, Steinacker P (2016) Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Annals of neurology 79 (1): 152– 8. doi: 10.1002/ana.24552. 26528863 · DOI
  21. [150]Rohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A, Toombs J, Druyeh R, Cardoso MJ, Ourselin S (2016) Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology 87 (13): 1329– 36. doi: 10.1212/WNL.0000000000003154. 27581216 PMC5047041 · DOI
  22. [153]Traenka C, Disanto G, Seiffge DJ, Gensicke H, Hert L, Grond-Ginsbach C, Peters N, Regeniter A, Kloss M, De Marchis GM (2015) Serum neurofilament light chain levels are associated with clinical characteristics and outcome in patients with cervical artery dissection. Cerebrovascular Diseases 40 (5–6): 222– 7. doi: 10.1159/000440774. 26418549 · DOI
  23. [154]Gattringer T, Pinter D, Enzinger C, Seifert-Held T, Kneihsl M, Fandler S, Pichler A, Barro C, Gröbke S, Voortman M (2017) Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology 89 (20): 2108– 2114. doi: 10.1212/WNL.0000000000004645. 29046363 PMC5711505 · DOI
  24. [155]Kuhle J, Gaiottino J, Leppert D, Petzold A, Bestwick JP, Malaspina A, Lu C-H, Dobson R, Disanto G, Norgren N (2015) Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome. Journal of neurology, neurosurgery, and psychiatry 86 (3): 273– 279. doi: 10.1136/jnnp-2013-307454. 24935984 · DOI
  25. [165]Jakobsson J, Bjerke M, Ekman CJ, Sellgren C, Johansson AG, Zetterberg H, Blennow K, Landén M (2014) Elevated concentrations of neurofilament light chain in the cerebrospinal fluid of bipolar disorder patients Neuropsychopharmacology 39(10): 2349– 56. doi: 10.1038/npp.2014.81. 24694925 PMC4138743 · DOI
  26. [167]Isgren A, Sellgren C, Ekman C-J, Holmén-Larsson J, Blennow K, Zetterberg H, Jakobsson J, Landén M (2017) Markers of neuroinflammation and neuronal injury in bipolar disorder: relation to prospective clinical outcomes. Brain, behavior, and immunity 65: 195– 201. doi: 10.1016/j.bbi.2017.05.002. 28483660 · DOI
  27. [175]Petzold A, Keir G, Green AJ, Giovannoni G, Thompson EJ (2003) A specific ELISA for measuring neurofilament heavy chain phosphoforms. J Immunol Methods 278 (1–2): 179– 190 12957406
  28. [198]Verde F, Steinacker P, Weishaupt JH, Kassubek J, Oeckl P, Halbgebauer S, Tumani H, von Arnim CAF, Dorst J, Feneberg E, Mayer B, Muller HP, Gorges M, Rosenbohm A, Volk AE, Silani V, Ludolph AC, Otto M (2019) Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. Journal of neurology, neurosurgery, and psychiatry 90 (2): 157– 164. doi: 10.1136/jnnp-2018-318704 30309882 · DOI

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Authors
Alirezaei, Z., Pourhanifeh, M. H., Borran, S., Nejati, M., Mirzaei, H., & Hamblin, M. R.
Affiliations
  • Isfahan University of Medical Sciences (IR)
  • Kashan University of Medical Sciences (IR)
  • Shahid Beheshti University (IR)
  • Harvard University (US)
Corresponding author
  • Mirzaei, Hamed
  • Hamblin, Michael R.
Venue
Molecular Neurobiology
Published
2019-08-05
Volume
57
Issue
1
Pages
469-491
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
OpenAlex
W2966118960
Cited by
142
References
186
Citations by year
2026: 33 · 2025: 34 · 2024: 16 · 2023: 18 · 2022: 21 · 2021: 9 · 2020: 10 · 2019: 1
FWCI
1.39
Type
journal article
Language
en
Open access
Locations
  • Molecular Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI050875, R21AI121700)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
neurofilament light chain, biomarkers, neurodegenerative diseases, cerebrospinal fluid, serum biomarkers, magnetic resonance imaging, diffusion tensor imaging, axonal injury, neuroimaging biomarkers, early diagnosis, central nervous system disorders
MeSH terms
Animals, Central Nervous System Diseases, Humans, Magnetic Resonance Imaging, Models, Biological, Solubility, Biomarkers, Neurofilament Proteins

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