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Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases

Karlsson, Linda LU orcid ; Vogel, Jacob LU ; Arvidsson, Ida LU orcid ; Åström, Kalle LU orcid ; Janelidze, Shorena LU ; Blennow, Kaj LU ; Palmqvist, Sebastian LU orcid ; Stomrud, Erik LU orcid ; Mattsson-Carlgren, Niklas LU orcid and Hansson, Oskar LU orcid (2024) In Nature Communications 15(1).
Abstract

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing... (More)

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
15
issue
1
article number
3676
publisher
Nature Publishing Group
external identifiers
  • pmid:38693142
  • scopus:85191724484
ISSN
2041-1723
DOI
10.1038/s41467-024-47971-5
language
English
LU publication?
yes
id
ed785bd7-5deb-4714-a6b8-4e4a4f33d9be
date added to LUP
2024-07-22 15:56:47
date last changed
2024-09-02 19:15:30
@article{ed785bd7-5deb-4714-a6b8-4e4a4f33d9be,
  abstract     = {{<p>Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.</p>}},
  author       = {{Karlsson, Linda and Vogel, Jacob and Arvidsson, Ida and Åström, Kalle and Janelidze, Shorena and Blennow, Kaj and Palmqvist, Sebastian and Stomrud, Erik and Mattsson-Carlgren, Niklas and Hansson, Oskar}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-47971-5}},
  doi          = {{10.1038/s41467-024-47971-5}},
  volume       = {{15}},
  year         = {{2024}},
}