Neurofilaments: neurobiological foundations for biomarker applications

Author:

Gafson Arie R1,Barthélemy Nicolas R2,Bomont Pascale3,Carare Roxana O4,Durham Heather D5,Julien Jean-Pierre67,Kuhle Jens8,Leppert David8,Nixon Ralph A9101112,Weller Roy O4,Zetterberg Henrik13141516,Matthews Paul M117ORCID

Affiliation:

1. Department of Brain Sciences, Imperial College, London, UK

2. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA

3. ATIP-Avenir team, INM, INSERM, Montpellier University, Montpellier, France

4. Clinical Neurosciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK

5. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Québec, Canada

6. Department of Psychiatry and Neuroscience, Laval University, Quebec, Canada

7. CERVO Brain Research Center, 2601 Chemin de la Canardière, Québec, QC, G1J 2G3, Canada

8. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland

9. Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, 10962, USA

10. Departments of Psychiatry, New York University School of Medicine, New York, NY, 10016, USA

11. Neuroscience Institute, New York University School of Medicine, New York, NY, 10016, USA

12. Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA

13. University College London Queen Square Institute of Neurology, London, UK

14. UK Dementia Research Institute at University College London, London, UK

15. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden

16. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

17. UK Dementia Research Institute at Imperial College, London

Abstract

AbstractInterest 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.

Funder

Dementia Research Institute at Imperial College

INSERM

Association Française contre les Myopathies

Alzheimer’s Research UK

National Institute on Aging

Swedish Research Council

European Research Council

Swedish State Support for Clinical Research

Swedish Brain Foundation

Dementia Research Institute

Edmond J Safra Foundation and Lily Safra

Imperial College Healthcare Trust

National Institute for Health Research

NIHR

Biomedical Research Centre

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

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