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Neurofilament light protein in CSF and blood is associated with neurodegeneration and disease severity in Huntington's disease

Soylu-Kucharz, Rana LU ; Sandelius, Åsa; Sjögren, Marie LU ; Blennow, Kaj LU ; Wild, Edward J.; Zetterberg, Henrik LU and Björkqvist, Maria LU (2017) In Scientific Reports 7(1).
Abstract

There is an unmet need to reliably and non-invasively monitor disease progression in preclinical Huntington's disease (HD) models. As a marker of axonal damage, neurofilament light chain (NfL) has been suggested a marker for neurodegeneration. NfL concentrations in blood and CSF were recently shown to have prognostic value for clinical HD progression and brain atrophy. We therefore hypothesized that CSF and blood NfL concentrations could be useful preclinical HD markers, reflecting underlying pathology. To test our hypothesis we utilized the R6/2 mouse model of HD and measured NfL concentrations in CSF and serum using the ultrasensitive Single molecule array (Simoa) platform. In addition, we assessed HD mouse disease characteristics. We... (More)

There is an unmet need to reliably and non-invasively monitor disease progression in preclinical Huntington's disease (HD) models. As a marker of axonal damage, neurofilament light chain (NfL) has been suggested a marker for neurodegeneration. NfL concentrations in blood and CSF were recently shown to have prognostic value for clinical HD progression and brain atrophy. We therefore hypothesized that CSF and blood NfL concentrations could be useful preclinical HD markers, reflecting underlying pathology. To test our hypothesis we utilized the R6/2 mouse model of HD and measured NfL concentrations in CSF and serum using the ultrasensitive Single molecule array (Simoa) platform. In addition, we assessed HD mouse disease characteristics. We found robust increases of NfL in CSF and serum in R6/2 mice compared to wild-type littermates. CSF and serum concentrations of NfL were significantly correlated, suggesting similar marker potential of serum NfL. CSF and serum concentrations of NfL correlated with disease severity, as assessed by striatal volume and body weight loss. We here provide evidence that CSF and blood NfL concentrations can be used as accessible and reliable pre-clinical HD markers. This will be of potential use for monitoring HD mouse model disease progression and evaluating preclinical disease-modifying treatment response.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
7
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85032508197
  • wos:000413816000044
ISSN
2045-2322
DOI
10.1038/s41598-017-14179-1
language
English
LU publication?
yes
id
8cba97ff-3870-48a0-a8f6-8c6907ad9af1
date added to LUP
2017-11-07 12:30:25
date last changed
2018-04-29 04:43:33
@article{8cba97ff-3870-48a0-a8f6-8c6907ad9af1,
  abstract     = {<p>There is an unmet need to reliably and non-invasively monitor disease progression in preclinical Huntington's disease (HD) models. As a marker of axonal damage, neurofilament light chain (NfL) has been suggested a marker for neurodegeneration. NfL concentrations in blood and CSF were recently shown to have prognostic value for clinical HD progression and brain atrophy. We therefore hypothesized that CSF and blood NfL concentrations could be useful preclinical HD markers, reflecting underlying pathology. To test our hypothesis we utilized the R6/2 mouse model of HD and measured NfL concentrations in CSF and serum using the ultrasensitive Single molecule array (Simoa) platform. In addition, we assessed HD mouse disease characteristics. We found robust increases of NfL in CSF and serum in R6/2 mice compared to wild-type littermates. CSF and serum concentrations of NfL were significantly correlated, suggesting similar marker potential of serum NfL. CSF and serum concentrations of NfL correlated with disease severity, as assessed by striatal volume and body weight loss. We here provide evidence that CSF and blood NfL concentrations can be used as accessible and reliable pre-clinical HD markers. This will be of potential use for monitoring HD mouse model disease progression and evaluating preclinical disease-modifying treatment response.</p>},
  articleno    = {14114},
  author       = {Soylu-Kucharz, Rana and Sandelius, Åsa and Sjögren, Marie and Blennow, Kaj and Wild, Edward J. and Zetterberg, Henrik and Björkqvist, Maria},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Neurofilament light protein in CSF and blood is associated with neurodegeneration and disease severity in Huntington's disease},
  url          = {http://dx.doi.org/10.1038/s41598-017-14179-1},
  volume       = {7},
  year         = {2017},
}