IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47971-5.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47971-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-47971-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Furqan Dar & Samuel R. Cohen & Diana M. Mitrea & Aaron H. Phillips & Gergely Nagy & Wellington C. Leite & Christopher B. Stanley & Jeong-Mo Choi & Richard W. Kriwacki & Rohit V. Pappu, 2024. "Biomolecular condensates form spatially inhomogeneous network fluids," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. López Pérez, Mario & Mansilla Corona, Ricardo, 2022. "Ordinal synchronization and typical states in high-frequency digital markets," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 598(C).
    3. Jessica M. Vanslambrouck & Sean B. Wilson & Ker Sin Tan & Ella Groenewegen & Rajeev Rudraraju & Jessica Neil & Kynan T. Lawlor & Sophia Mah & Michelle Scurr & Sara E. Howden & Kanta Subbarao & Melissa, 2022. "Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    4. Dennis Bontempi & Leonard Nuernberg & Suraj Pai & Deepa Krishnaswamy & Vamsi Thiriveedhi & Ahmed Hosny & Raymond H. Mak & Keyvan Farahani & Ron Kikinis & Andrey Fedorov & Hugo J. W. L. Aerts, 2024. "End-to-end reproducible AI pipelines in radiology using the cloud," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    5. Lauren L. Porter & Allen K. Kim & Swechha Rimal & Loren L. Looger & Ananya Majumdar & Brett D. Mensh & Mary R. Starich & Marie-Paule Strub, 2022. "Many dissimilar NusG protein domains switch between α-helix and β-sheet folds," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Oren Amsalem & Hidehiko Inagaki & Jianing Yu & Karel Svoboda & Ran Darshan, 2024. "Sub-threshold neuronal activity and the dynamical regime of cerebral cortex," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Matthew Rosenblatt & Link Tejavibulya & Rongtao Jiang & Stephanie Noble & Dustin Scheinost, 2024. "Data leakage inflates prediction performance in connectome-based machine learning models," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Sayedali Shetab Boushehri & Katharina Essig & Nikolaos-Kosmas Chlis & Sylvia Herter & Marina Bacac & Fabian J. Theis & Elke Glasmacher & Carsten Marr & Fabian Schmich, 2023. "Explainable machine learning for profiling the immunological synapse and functional characterization of therapeutic antibodies," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Khaled Akkad & David He, 2023. "A dynamic mode decomposition based deep learning technique for prognostics," Journal of Intelligent Manufacturing, Springer, vol. 34(5), pages 2207-2224, June.
    10. Romain Fournier & Zoi Tsangalidou & David Reich & Pier Francesco Palamara, 2023. "Haplotype-based inference of recent effective population size in modern and ancient DNA samples," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    11. Laura Portell & Sergi Morera & Helena Ramalhinho, 2022. "Door-to-Door Transportation Services for Reduced Mobility Population: A Descriptive Analytics of the City of Barcelona," IJERPH, MDPI, vol. 19(8), pages 1-20, April.
    12. Caroline Haimerl & Douglas A. Ruff & Marlene R. Cohen & Cristina Savin & Eero P. Simoncelli, 2023. "Targeted V1 comodulation supports task-adaptive sensory decisions," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    13. Pullinger, Martin & Zapata-Webborn, Ellen & Kilgour, Jonathan & Elam, Simon & Few, Jessica & Goddard, Nigel & Hanmer, Clare & McKenna, Eoghan & Oreszczyn, Tadj & Webb, Lynda, 2024. "Capturing variation in daily energy demand profiles over time with cluster analysis in British homes (September 2019 – August 2022)," Applied Energy, Elsevier, vol. 360(C).
    14. Matthias Wagener & Andriette Bekker & Mohammad Arashi, 2021. "Mastering the Body and Tail Shape of a Distribution," Mathematics, MDPI, vol. 9(21), pages 1-22, October.
    15. Gallo Cassarino, Tiziano & Barrett, Mark, 2022. "Meeting UK heat demands in zero emission renewable energy systems using storage and interconnectors," Applied Energy, Elsevier, vol. 306(PB).
    16. Maren Schnieder, 2023. "Ebike Sharing vs. Bike Sharing: Demand Prediction Using Deep Neural Networks and Random Forests," Sustainability, MDPI, vol. 15(18), pages 1-15, September.
    17. Gabriele Orlando & Daniele Raimondi & Ramon Duran-Romaña & Yves Moreau & Joost Schymkowitz & Frederic Rousseau, 2022. "PyUUL provides an interface between biological structures and deep learning algorithms," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    18. Hazal Colak Oz & Çiçek Güven & Gonzalo Nápoles, 2023. "School dropout prediction and feature importance exploration in Malawi using household panel data: machine learning approach," Journal of Computational Social Science, Springer, vol. 6(1), pages 245-287, April.
    19. Vincent Wagner & Nicole Erika Radde, 2021. "SiCaSMA: An Alternative Stochastic Description via Concatenation of Markov Processes for a Class of Catalytic Systems," Mathematics, MDPI, vol. 9(10), pages 1-13, May.
    20. L. Mathur & B. Szalai & N. H. Du & R. Utharala & M. Ballinger & J. J. M. Landry & M. Ryckelynck & V. Benes & J. Saez-Rodriguez & C. A. Merten, 2022. "Combi-seq for multiplexed transcriptome-based profiling of drug combinations using deterministic barcoding in single-cell droplets," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47971-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.