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Neurofilaments: neurobiological foundations for biomarker applications

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
0006-8950
1975–1998
Gafson, Arie R.
b0ec67df-786b-4788-ac09-47c0f65270a3
Barthélemy, Nicolas R.
dc169a5d-2c1e-466b-80a1-92ee5556493b
Bomont, Pascale
336e1e2b-4f9c-4592-afee-4fcb1fce0aee
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Durham, Heather D.
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Julien, Jean-Pierre
2a8a375d-0c00-4798-81b7-c4efd61ac893
Kuhle, Jens
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Leppert, David
2cfb124d-178c-4ad3-8b43-5b7fec4c61a7
Nixon, Ralph A.
ce6773f8-a657-4764-a6c7-4a1d7b4c275a
Weller, Roy O.
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Zetterberg, Henrik
65e1750c-2467-4f02-ac28-e0e41c3a76b2
Matthews, Paul M.
8c37e5aa-c28d-46ea-ab4a-e947d36fedf7
Gafson, Arie R.
b0ec67df-786b-4788-ac09-47c0f65270a3
Barthélemy, Nicolas R.
dc169a5d-2c1e-466b-80a1-92ee5556493b
Bomont, Pascale
336e1e2b-4f9c-4592-afee-4fcb1fce0aee
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Durham, Heather D.
6c56083e-5e3b-4067-a06c-c25f7f1a785e
Julien, Jean-Pierre
2a8a375d-0c00-4798-81b7-c4efd61ac893
Kuhle, Jens
20bae556-587b-4838-a6e6-29998763f0e0
Leppert, David
2cfb124d-178c-4ad3-8b43-5b7fec4c61a7
Nixon, Ralph A.
ce6773f8-a657-4764-a6c7-4a1d7b4c275a
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Zetterberg, Henrik
65e1750c-2467-4f02-ac28-e0e41c3a76b2
Matthews, Paul M.
8c37e5aa-c28d-46ea-ab4a-e947d36fedf7

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), 1975–1998. (doi:10.1093/brain/awaa098).

Record type: Article

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 - Version of Record
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More information

Accepted/In Press date: 20 January 2020
e-pub ahead of print date: 14 May 2020
Published date: 1 July 2020
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
ORCID for Roxana-Octavia Carare: ORCID iD orcid.org/0000-0001-6458-3776

Catalogue record

Date deposited: 11 Aug 2020 16:31
Last modified: 22 Nov 2021 02:43

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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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