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

Author

Listed:
  • Linda Karlsson

    (Lund University)

  • Jacob Vogel

    (Lund University
    Lund University)

  • Ida Arvidsson

    (Lund University)

  • Kalle Åström

    (Lund University)

  • Shorena Janelidze

    (Lund University)

  • Kaj Blennow

    (University of Gothenburg
    Sahlgrenska University Hospital)

  • Sebastian Palmqvist

    (Lund University
    Skåne University Hospital)

  • Erik Stomrud

    (Lund University
    Skåne University Hospital)

  • Niklas Mattsson-Carlgren

    (Lund University
    Skåne University Hospital)

  • Oskar Hansson

    (Lund University
    Skåne University Hospital)

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 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.

Suggested Citation

  • Linda Karlsson & Jacob Vogel & Ida Arvidsson & Kalle Åström & Shorena Janelidze & Kaj Blennow & Sebastian Palmqvist & Erik Stomrud & Niklas Mattsson-Carlgren & Oskar Hansson, 2024. "Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47971-5
    DOI: 10.1038/s41467-024-47971-5
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    References listed on IDEAS

    as
    1. Charles R. Harris & K. Jarrod Millman & Stéfan J. Walt & Ralf Gommers & Pauli Virtanen & David Cournapeau & Eric Wieser & Julian Taylor & Sebastian Berg & Nathaniel J. Smith & Robert Kern & Matti Picu, 2020. "Array programming with NumPy," Nature, Nature, vol. 585(7825), pages 357-362, September.
    2. Alexa Pichet Binette & Nicolai Franzmeier & Nicola Spotorno & Michael Ewers & Matthias Brendel & Davina Biel & Olof Strandberg & Shorena Janelidze & Sebastian Palmqvist & Niklas Mattsson-Carlgren & Ru, 2022. "Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
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