Increased cerebrospinal fluid levels of neurofilament protein in progressive supranuclear palsy and multiple‐system atrophy compared with Parkinson's disease

Holmberg, Björn; Rosengren, Lars; Karlsson, Jan‐Erik; Johnels, Bo

doi:10.1002/mds.870130116

Cited by 130 publications

(83 citation statements)

References 27 publications

(2 reference statements)

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“…97,108,113 In contrast, GFAP levels were comparable in PSP, PD and MSA patients. 98 In summary, based on these studies, both CSF S100B and GFAP analysis do not seem to be helpful in the diagnosis of neurodegenerative diseases, except for CJD.…”

Section: 107mentioning

confidence: 88%

Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases

Verbeek¹,

Jong²,

Kremer³

2003

Ann Clin Biochem

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Neurodegenerative disorders have traditionally been classi ed according to clinical criteria, e.g. as dementia syndromes (the best known is Alzheimer's disease) or as movement disorders (e.g. Parkinson's disease). Another subdivision is based on recent insights into the respective pathogenetic mechanisms, leading to the recognition of so-called tauopathies and a-synucleinopathies. It is this increased knowledge of the underlying (neuro)pathological mechanisms that has sparked interest in studies aimed at the identi cation of disease-speci c biomarkers in cerebrospinal uid (CSF) for this eld of neurological disorders. This review deals with the recent progress that has been made in identi cation, quanti cation and subsequent validation of brain-speci c proteins in CSF for the diagnosis of various neurodegenerative disorders. Development of disease-speci c CSF biomarkers will undoubtedly add to the process of differential diagnosis early in the course of the disease.

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Section: 107mentioning

confidence: 88%

Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases

Verbeek¹,

Jong²,

Kremer³

2003

Ann Clin Biochem

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“…24 Furthermore, higher levels of NFL have been reported in MSA-P relative to Parkinson disease. 25,26 Therefore, NF proteins could be regarded as biomarkers of degeneration of (especially large myelinated) axons. Axonal degeneration within, for example, the pyramidal tracts could thus result in higher NF protein levels in the CSF.…”

Section: Figure Csf Levels Of Neurofilament Light Chain (A) Neurofimentioning

confidence: 99%

CSF analysis differentiates multiple-system atrophy from idiopathic late-onset cerebellar ataxia

Abdo

Warrenburg²,

Munneke³

et al. 2006

Neurology

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Abstract-Background: Differentiating idiopathic late-onset cerebellar ataxia (ILOCA) from ataxia due to the cerebellar subtype of multiple-system atrophy (MSA-C) can be difficult in the early stages of the disease Methods: The authors analyzed the levels of various CSF biomarkers in 27 patients with MSA-C and 18 patients with ILOCA and obtained cut-off points for each potential biomarker to differentiate MSA-C from ILOCA. Results: Increased levels of neurofilament light chain (NFL) and neurofilament heavy chain (NFHp35) and decreased levels of the neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindoleaceticacid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) were observed in MSA-C compared with ILOCA patients. Receiver operating characteristic analysis showed high sensitivity and specificity levels for NFL, NFHp35, and MHPG analysis. At a cut-off of 24.4 ng/L for the NFL analysis, a sensitivity of 79% and a specificity of 94% were obtained for differentiating MSA-C from ILOCA. At a cut-off point for NFHp35 of 129.5 ng/L, sensitivity was 87% and specificity 83%. Analysis of MHPG levels (cut-off 42.5 nM) resulted in a sensitivity of 86% with a specificity of 75%. A multivariate logistic regression model selected NFL, MHPG, and tau as independent predictive biomarkers that separated the MSA-C and ILOCA groups. Conclusions: Increased levels of neurofilament light chain and tau and decreased levels of 3-methoxy-4-hydroxyphenylethyleneglycol were associated with high accuracy levels in differentiating the cerebellar subtype of multiple-system atrophy from idiopathic late-onset cerebellar ataxia (LOCA). CSF analysis may thus serve as a useful tool in early diagnostic differentiation of LOCA.

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“…High CSF NfL and NfH levels were first described by Holmberg et al [27] in patients with multi-system atrophy (MSA). Later studies showed that this was more marked in patients with the cerebellar variant [28,29] .…”

Section: Csf Nf Levels In the Wider Field Of Neurodegenerative Diseasesmentioning

confidence: 99%

“…Again, the CSF Nf levels observed were considerably higher, similar to those in patients suffering from a neurodegenerative dementia [7,8,[11][12][13][14][15][17][18][19][20] . Progressive supranuclear palsy (PSP) is another disorder with pathological CSF NfH and NfL levels [27,28] . Patients with Parkinson's disease (PD) or corticobasal degeneration (CBD) also had higher CSF NfH levels compared to controls.…”

Section: Csf Nf Levels In the Wider Field Of Neurodegenerative Diseasesmentioning

confidence: 99%

A Systematic Review and Meta-Analysis of CSF Neurofilament Protein Levels as Biomarkers in Dementia

et al. 2007

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Background: Loss of cortical neurons is a key pathological feature in neurodegenerative dementias. Cerebrospinal fluid (CSF) neurofilaments (Nf) are a biomarker for neuronal death and axonal loss. Objective: To perform a meta-analysis to investigate the value of CSF Nf levels for the laboratory-supported differential diagnosis of neurodegenerative dementias. Methods: A systematic review and meta-analysis of studies on CSF Nf heavy (NfH) and light (NfL) levels in patients with dementia. The dementia subgroups analysed were Alzheimer (AD), frontotemporal lobe dementia (FTLD), vascular dementia (SVD), minimal cognitive deficit (MCI). Results: We identified 12 studies on CSF NfH and NfL levels which met the inclusion criteria and 11 were of a quality good enough to be used in this meta-analysis. CSF data was available on 818 patients (306 AD, 106 SVD, 98 FTLD, 25 MCI, 283 controls). Overall CSF NfH and NfL levels were higher in patients with AD, FTLD and SVD when compared to controls. The size of the effect ranged from 0.71 to 1.38. The strongest effect was observed for the comparison of FTLD patients with controls, both for NfL (1.38) and NfH (0.74). CSF NfL were also able to separate patients with FTLD from those with AD. Conclusion: At present we cannot recommend CSF NfH and NfL levels for use as a screening test in the diagnosis of dementia because of the rather small effect size. However, both neurofilament proteins may be of value for targeted investigation of some patients with FTLD, SVD and AD.

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Increased cerebrospinal fluid levels of neurofilament protein in progressive supranuclear palsy and multiple‐system atrophy compared with Parkinson's disease

Cited by 130 publications

References 27 publications

Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases

Brain-specific proteins in cerebrospinal fluid for the diagnosis of neurodegenerative diseases

CSF analysis differentiates multiple-system atrophy from idiopathic late-onset cerebellar ataxia

A Systematic Review and Meta-Analysis of CSF Neurofilament Protein Levels as Biomarkers in Dementia

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