Abstract

Neurofilaments (NFs) are quickly becoming the biomarkers of choice in the field of neurology, suggesting their use as an unspecific screening marker, much like the use of elevated plasma C-reactive protein (CRP) in other fields. With sensitive techniques being readily available, evidence is growing regarding the diagnostic and prognostic value of NFs in many neurological disorders. Here, we review the latest literature on the structure and function of NFs and report the strengths and pitfalls of NFs as markers of neurodegeneration in the context of neurological diseases of the central and peripheral nervous systems.

Highlights

  • The interest in neurofilaments (NFs) and their role as disease biomarkers has grown immensely in recent years

  • NFs were first tested as possible biomarkers by Rosengren et al, who detected an increase in cerebrospinal fluid (CSF) NF-light chain (NF-L) in patients with Alzheimer’s disease (AD)

  • NFs move to the CSF and subsequently to the blood, where their levels can be measured in serum and plasma and correlated to the extent of axonal damage or neurodegeneration (Figure 1 and Table 1)

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Summary

Introduction

The interest in neurofilaments (NFs) and their role as disease biomarkers has grown immensely in recent years. Alzheimer’s disease; AIS, acute ischemic stroke; ALS, amyotrophic lateral sclerosis; aMCI, amnestic mild cognitive impairment; aSAH, aneurysmal subarachnoid hemorrhage; CA, cardiac arrest; CADASIL, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CBS, corticobasal syndrome; CeAD, cervical artery dissection; CIDP, chronic inflammatory demyelinating polyneuropathy; CMT, Charcot–Marie–Tooth; CSF, cerebrospinal fluid; ECL, electrochemiluminescence; FTD, frontotemporal dementia; GBS, Guillain–Barré syndrome; GCS, Glasgow Coma Scale; HD, Huntington’s disease; HHT, huntingtin; HS, hemorrhagic stroke; MCI, mild cognitive impairment; MMN, multifocal motor neuropathy; MND, motor neuron disease; MS, multiple sclerosis; MSA, multiple system atrophy; NF-M, neurofilament medium chain; ON, optic neuritis; PD, Parkinson’s disease; pNF-L, plasma neurofilament light chain; p-pNF-H, plasma phosphorylated neurofilament heavy chain; PSP, progressive supranuclear palsy; ROSC, return of spontaneous circulation; RSSI, recent small subcortical infarcts; SAH, subarachnoid hemorrhage; SCI, spinal cord injury; s-pNF-H, serum-phosphorylated neurofilament heavy chain; Simoa, single molecule array; sNF-L, serum neurofilament light chain; SVD, small vessel disease; TIA, transient ischemic attack; WMH, white matter hyperintensities; WML, white matter lesions

75 CMT and 67 controls pNF-L
68 ON patients
35 HD patients and 35 controls
22 AIS patients enrolled within 6–24 h after symptom onset sNF-H
53 SVD patients
72 TBI and 35 controls
21 CA patients 2 weeks post-CA and 21 controls
26 ROSC CA and 26 non-ROSC CA patients on admission
The Structure and Function of Neurofilament
Peripheral Neuropathy
Motor Neuron Disease
Multiple Sclerosis
Alzheimer’s Disease
Huntington’s Disease
Parkinson’s Disease and Parkinsonian Disorders
Stroke
Traumatic Axonal Injury
Cardiac Arrest
3.10. Delirium
Findings
Discussion
Conclusions
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