Neurofilaments: neurobiological foundations for biomarker applications
Neurofilaments: neurobiological foundations for biomarker applications
Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood. This is in the context of a growing appreciation for the complexity of the neurobiology of neurofilaments, new recognition of specialized roles for neurofilaments in synapses and a developing understanding of mechanisms responsible for their turnover. Here we will review the neurobiology of neurofilament proteins, describing current understanding of their structure and function, including recently discovered evidence for their roles in synapses. We will explore emerging understanding of the mechanisms of neurofilament degradation and clearance and review new methods for future elucidation of the kinetics of their turnover in humans. Primary roles of neurofilaments in the pathogenesis of human diseases will be described. With this background, we then will review critically evidence supporting use of neurofilament concentration measures as biomarkers of neuronal injury or degeneration. Finally, we will reflect on major challenges for studies of the neurobiology of intermediate filaments with specific attention to identifying what needs to be learned for more precise use and confident interpretation of neurofilament measures as biomarkers of neurodegeneration.
biomarkers, neurodegeneration, neurofilaments, neuroinflammation, traumatic brain injury
1975–1998
Gafson, Arie R.
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Barthélemy, Nicolas R.
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Bomont, Pascale
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Carare, Roxana-Octavia
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Durham, Heather D.
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Julien, Jean-Pierre
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Kuhle, Jens
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Leppert, David
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Nixon, Ralph A.
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Weller, Roy O.
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Zetterberg, Henrik
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Matthews, Paul M.
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1 July 2020
Gafson, Arie R.
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Barthélemy, Nicolas R.
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Bomont, Pascale
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Carare, Roxana-Octavia
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Durham, Heather D.
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Julien, Jean-Pierre
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Kuhle, Jens
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Leppert, David
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Nixon, Ralph A.
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Weller, Roy O.
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Zetterberg, Henrik
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Matthews, Paul M.
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Gafson, Arie R., Barthélemy, Nicolas R., Bomont, Pascale, Carare, Roxana-Octavia, Durham, Heather D., Julien, Jean-Pierre, Kuhle, Jens, Leppert, David, Nixon, Ralph A., Weller, Roy O., Zetterberg, Henrik and Matthews, Paul M.
(2020)
Neurofilaments: neurobiological foundations for biomarker applications.
Brain, 143 (7), .
(doi:10.1093/brain/awaa098).
Abstract
Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood. This is in the context of a growing appreciation for the complexity of the neurobiology of neurofilaments, new recognition of specialized roles for neurofilaments in synapses and a developing understanding of mechanisms responsible for their turnover. Here we will review the neurobiology of neurofilament proteins, describing current understanding of their structure and function, including recently discovered evidence for their roles in synapses. We will explore emerging understanding of the mechanisms of neurofilament degradation and clearance and review new methods for future elucidation of the kinetics of their turnover in humans. Primary roles of neurofilaments in the pathogenesis of human diseases will be described. With this background, we then will review critically evidence supporting use of neurofilament concentration measures as biomarkers of neuronal injury or degeneration. Finally, we will reflect on major challenges for studies of the neurobiology of intermediate filaments with specific attention to identifying what needs to be learned for more precise use and confident interpretation of neurofilament measures as biomarkers of neurodegeneration.
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Neurofilament Review published BRAIN 2020
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Accepted/In Press date: 20 January 2020
e-pub ahead of print date: 14 May 2020
Published date: 1 July 2020
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Funding Information:
This review was written following an open workshop concerning neurofilament biology and use as biomarker including all of the co-authors that was held at Imperial College London on 18 Nov 2018 (https://www.imperial.ac.uk/demen tia-research-institute/seminars-events/past-events/neurofilaments-as-a-biomarker/). The workshop was initiated and planned by Prof. Paul Matthews and Prof. Henrik Zetterberg. Funding for the workshop was provided by the UK Dementia Research Institute at Imperial College and an educational grant provided by Biogen. P.B.'s laboratory was funded for neurofilament biology by INSERM (ATIP-Avenir program) and the Association Fran?aise contre les Myopathies (AFM). R.O.C. and R.O.W.'s laboratory was funded by Alzheimer's Research UK (ARUK) and Biogen. The R.A.N. laboratory has been supported by National Institute on Aging (R01AG0560; P01AG017617). H.Z. is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Swedish Brain Foundation (FO2019-0228) and the UK Dementia Research Institute at UCL. P.M.M. has been in receipt of generous personal and research support from the Edmond J Safra Foundation and Lily Safra, the Imperial College Healthcare Trust - National Institute for Health Research (NIHR) Biomedical Research Centre, an NIHR Senior Investigator's Award, the Medical Research Council and the UK Dementia Research Institute, which is supported by the Medical Research Council, The Alzheimer's Society and Alzheimer's Research UK.
Copyright: The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
Keywords:
biomarkers, neurodegeneration, neurofilaments, neuroinflammation, traumatic brain injury
Identifiers
Local EPrints ID: 443109
URI: http://eprints.soton.ac.uk/id/eprint/443109
ISSN: 0006-8950
PURE UUID: 74491cab-1e75-468c-8a6a-068acc8acfac
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Date deposited: 11 Aug 2020 16:31
Last modified: 17 Mar 2024 02:48
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Contributors
Author:
Arie R. Gafson
Author:
Nicolas R. Barthélemy
Author:
Pascale Bomont
Author:
Heather D. Durham
Author:
Jean-Pierre Julien
Author:
Jens Kuhle
Author:
David Leppert
Author:
Ralph A. Nixon
Author:
Roy O. Weller
Author:
Henrik Zetterberg
Author:
Paul M. Matthews
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