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Neurofilament Light Chain as a Biomarker in Cerebral Small-Vessel Disease

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Abstract

Neurofilament light chain is part of the neuroaxonal cytoskeleton and upon disease-related neuroaxonal damage, it is released to the extracellular space and, based on modern highly sensitive assays, can also be detected in the peripheral blood. Thus, neurofilament light chain in the blood is an emerging marker of neurological disease, including age-related conditions, such as neurodegenerative but also neurovascular diseases. Recently, blood neurofilament light chain has been shown to serve as a potentially interesting marker of disease burden and prognostication also in cerebral small-vessel disease, a condition that is highly prevalent in elderly subjects. Small-vessel disease is a progressive condition, often related to common vascular risk factors such as arterial hypertension and is an important cause of stroke, vascular cognitive impairment, and dementia. As an age-dependent condition, small-vessel disease may occur concomitantly with neurodegenerative diseases, with both conditions having a potential impact on clinical status or cognitive performance. The aim of the present article is to give an overview on the current knowledge on neurofilament light chain as a disease or progression marker in small-vessel disease.

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References

  1. Norgren N, Rosengren L, Stigbrand T. Elevated neurofilament levels in neurological diseases. Brain Res. 2003;987(1):25–31.

    Article  CAS  Google Scholar 

  2. Duering M, Konieczny MJ, Tiedt S, et al. Serum neurofilament light chain levels are related to small vessel disease burden. J Stroke. 2018;20(2):228–38.

    Article  Google Scholar 

  3. Peters N, van Leijsen E, Tuladhar AM, et al. Serum neurofilament light chain is associated with incident lacunes in progressive cerebral small vessel disease. J Stroke. 2020;22(3):369–76.

    Article  Google Scholar 

  4. Gendron TF, Badi MK, Heckman MG, et al. Plasma neurofilament light predicts mortality in patients with stroke. Sci Transl Med. 2020. https://doi.org/10.1126/scitranslmed.aay1913.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wang SY, Chen W, Xu W, et al. Neurofilament light chain in cerebrospinal fluid and blood as a biomarker for neurodegenerative diseases: a systematic review and meta-analysis. J Alzheimers Dis. 2019;72(4):1353–61.

    Article  Google Scholar 

  6. Disanto G, Barro C, Benkert P, Naegelin Y, Schadelin S, Giardiello A, et al. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857–70.

    Article  CAS  Google Scholar 

  7. Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, et al. Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology. 2015;84:2247–57.

    Article  CAS  Google Scholar 

  8. Mattsson N, Andreasson U, Zetterberg H, Blennow K, Alzheimer’s Disease Neuroimaging Initiative. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2017;74:557–66.

    Article  Google Scholar 

  9. Rohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A, et al. Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology. 2016;87:1329–36.

    Article  CAS  Google Scholar 

  10. Hansson O, Janelidze S, Hall S, Magdalinou N, Lees AJ, Andreasson U, et al. Blood-based NfL: a biomarker for differential diagnosis of parkinsonian disorder. Neurology. 2017;88(10):930–7.

    Article  CAS  Google Scholar 

  11. Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association between longitudinal plasma neurofilament light and neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2019;76:791–9.

    Article  Google Scholar 

  12. Feneberg E, Oeckl P, Steinacker P, Verde F, Barro C, Van Damme P, et al. Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology. 2018;90(1):e22-30.

    Article  CAS  Google Scholar 

  13. Tiedt S, Duering M, Barro C, Kaya AG, Boeck J, Bode FJ, et al. Serum neurofilament light: a biomarker of neuroaxonal injury after ischemic stroke. Neurology. 2018;91(14):e1338–47.

    Article  CAS  Google Scholar 

  14. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689–701.

    Article  Google Scholar 

  15. Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822–38.

    Article  Google Scholar 

  16. Hert L, Polymeris AA, Schaedelin S, et al. Small vessel disease is associated with an unfavourable outcome in stroke patients on oral anticoagulation. Eur Stroke J. 2020;5(1):63–72.

    Article  Google Scholar 

  17. Kuhle J, Barro C, Andreasson U, et al. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med. 2016;54(10):1655–61.

    Article  CAS  Google Scholar 

  18. Barro C, Zetterberg H. The blood biomarkers puzzle: a review of protein biomarkers in neurodegenerative diseases. J Neurosci Methods. 2021;361:109281.

    Article  CAS  Google Scholar 

  19. Gauthier A, Viel S, Perret M, et al. Comparison of Simoa™ and Ella™ to assess serum neurofilament-light chain in multiple sclerosis. Ann Clin Transl Neurol. 2021;8(5):1141–50.

    Article  CAS  Google Scholar 

  20. Khalil M, Pirpamer L, Hofer E, et al. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat Commun. 2020;11(1):812.

    Article  CAS  Google Scholar 

  21. Disanto G, Barro C, Benkert P, et al. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857–70.

    Article  CAS  Google Scholar 

  22. Zieren N, Duering M, Peters N, Reyes S, Jouvent E, Hervé D, et al. Education modifies the relation of vascular pathology to cognitive function: cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Neurobiol Aging. 2013;34:400–7.

    Article  Google Scholar 

  23. Charlton RA, Morris RG, Nitkunan A, Markus HS. The cognitive profiles of CADASIL and sporadic small vessel disease. Neurology. 2006;66:1523–6.

    Article  CAS  Google Scholar 

  24. Peters N, Opherk C, Danek A, Ballard C, Herzog J, Dichgans M. The pattern of cognitive performance in CADASIL: a monogenic condition leading to subcortical ischemic vascular dementia. Am J Psychiatry. 2005;162(11):2078–85.

    Article  Google Scholar 

  25. Gattringer T, Pinter D, Enzinger C, et al. Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology. 2017;89(20):2108–14.

    Article  Google Scholar 

  26. Ling Y, De Guio F, Duering M, Jouvent E, Hervé D, Godin O, et al. Predictors and clinical impact of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2017;48:283–9.

    Article  Google Scholar 

  27. Blanco-Rojas L, Arboix A, Canovas D, Grau-Olivares M, Oliva Morera JC, Parra O. Cognitive profile in patients with a first-ever lacunar infarct with and without silent lacunes: a comparative study. BMC Neurol. 2013;13:203.

    Article  Google Scholar 

  28. Pinter D, Gattringer T, Enzinger C, Seifert-Held T, Kneihsl M, Fandler S, et al. Longitudinal MRI dynamics of recent small subcortical infarcts and possible predictors. J Cereb Blood Flow Metab. 2019;39:1669–77.

    Article  Google Scholar 

  29. Pedersen A, Stanne TM, Nilsson S, Klasson S, Rosengren L, Holmegaard L, et al. Circulating neurofilament light in ischemic stroke: temporal profile and outcome prediction. J Neurol. 2019;266(11):2796–806.

    Article  CAS  Google Scholar 

  30. Wang P, Fan J, Yuan L, Nan Y, Nan S. Serum neurofilament light predicts severity and prognosis in patients with ischemic stroke. Neurotox Res. 2020;37(4):987–95.

    Article  CAS  Google Scholar 

  31. Korley FK, Goldstick J, Mastali M, Van Eyk JE, Barsan W, Meurer WJ, et al. Serum NfL (neurofilament light chain) levels and incident stroke in adults with diabetes mellitus. Stroke. 2019;50(7):1669–75.

    Article  CAS  Google Scholar 

  32. Chen CH, Cheng YW, Chen YF, Tang SC, Jeng JS. Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL. J Neuroinflammation. 2020;17(1):124.

    Article  CAS  Google Scholar 

  33. Egle M, Loubiere L, Maceski A, Kuhle J, Peters N, Markus HS. Neurofilament light chain predicts future dementia risk in cerebral small vessel disease. J Neurol Neurosurg Psychiatry. 2021;92(6):582–9.

    Article  Google Scholar 

  34. Baykara E, Gesierich B, Adam R, Tuladhar AM, Biesbroek JM, Koek HL, et al. A novel imaging marker for small vessel disease based on skeletonization of white matter tracts and diffusion histograms. Ann Neurol. 2016;80:581–92.

    Article  Google Scholar 

  35. Benjamin P, Zeestraten E, Lambert C, Ster IC, Williams OA, Lawrence AJ, et al. Progression of MRI markers in cerebral small vessel disease: sample size considerations for clinical trials. J Cereb Blood Flow Metab. 2016;36:228–40.

    Article  Google Scholar 

  36. Peters N, Holtmannspötter M, Opherk C, Gschwendtner A, Herzog J, Sämann P, et al. Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease. Neurology. 2006;66(10):1517–22.

    Article  CAS  Google Scholar 

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Acknowledgements

The author thanks all collaborators involved in the various research projects performed on blood NfL in the different SVD cohorts. The author also thanks all patients of the different SVD cohorts who participated in the various studies.

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Authors and Affiliations

  1. Stroke Center, Klinik Hirslanden, Zurich, Switzerland

    Nils Peters

  2. Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland

    Nils Peters

  3. Neurorehabilitation Unit, Felix Platter Hospital, University of Basel and University Center for Medicine of Aging, Basel, Switzerland

    Nils Peters

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Correspondence to Nils Peters.

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Peters, N. Neurofilament Light Chain as a Biomarker in Cerebral Small-Vessel Disease. Mol Diagn Ther 26, 1–6 (2022). https://doi.org/10.1007/s40291-021-00566-y

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