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CSF total tau as a proxy of synaptic degeneration

Author

Listed:
  • Carolina Soares

    (University of Pittsburgh
    Universidade Federal do Rio Grande do Sul)

  • Bruna Bellaver

    (University of Pittsburgh)

  • Pamela C. L. Ferreira

    (University of Pittsburgh)

  • Guilherme Povala

    (University of Pittsburgh)

  • Cristiano Schaffer Aguzzoli

    (University of Pittsburgh
    University of California
    PUCRS)

  • João Pedro Ferrari-Souza

    (University of Pittsburgh
    Universidade Federal do Rio Grande do Sul)

  • Hussein Zalzale

    (University of Pittsburgh)

  • Firoza Z. Lussier

    (University of Pittsburgh)

  • Francieli Rohden

    (University of Pittsburgh
    Universidade Federal do Rio Grande do Sul)

  • Sarah Abbas

    (University of Pittsburgh)

  • Guilherme Bauer-Negrini

    (University of Pittsburgh)

  • Douglas Teixeira Leffa

    (University of Pittsburgh)

  • Andréa Lessa Benedet

    (University of Gothenburg)

  • Rebecca Langhough

    (University of Wisconsin
    University of Wisconsin)

  • Tobey J. Betthauser

    (University of Wisconsin
    University of Wisconsin)

  • Bradley T. Christian

    (University of Wisconsin)

  • Rachael E. Wilson

    (University of Wisconsin
    University of Wisconsin)

  • Dana L. Tudorascu

    (University of Pittsburgh
    University of Pittsburgh)

  • Pedro Rosa-Neto

    (Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Ouest-de-l’Île-de-Montréal
    McGill University
    Montreal Neurological Institute-Hospital)

  • Thomas K. Karikari

    (University of Pittsburgh
    University of Gothenburg)

  • Henrik Zetterberg

    (University of Gothenburg
    University of Wisconsin
    Sahlgrenska University Hospital
    University College London Queen Square Institute of Neurology)

  • Kaj Blennow

    (University of Gothenburg
    Sahlgrenska University Hospital)

  • Eduardo R. Zimmer

    (Universidade Federal do Rio Grande do Sul
    PUCRS
    Hospital Moinhos de Vento
    Universidade Federal do Rio Grande do Sul)

  • Sterling C. Johnson

    (University of Wisconsin
    University of Wisconsin)

  • Tharick A. Pascoal

    (University of Pittsburgh
    University of Pittsburgh)

Abstract

Cerebrospinal fluid (CSF) total tau (t-tau) is considered a biomarker of neuronal degeneration alongside brain atrophy and fluid neurofilament light chain protein (NfL) in biomarker models of Alzheimer’s disease (AD). However, previous studies show that CSF t-tau correlates strongly with synaptic dysfunction/degeneration biomarkers like neurogranin (Ng) and synaptosomal-associated protein 25 (SNAP25). Here, we compare the association between CSF t-tau and synaptic degeneration and axonal/neuronal degeneration biomarkers in cognitively unimpaired and impaired groups from two independent cohorts. We observe a stronger correlation between CSF t-tau and synaptic biomarkers than neurodegeneration biomarkers in both groups. Synaptic biomarkers explain a greater proportion of variance in CSF t-tau levels compared to neurodegeneration biomarkers. Notably, CSF t-tau levels are elevated in individuals with abnormalities only in synaptic biomarkers, but not in individuals with abnormalities only in neurodegeneration biomarkers. Our findings suggest that CSF t-tau is a closer proxy for synaptic degeneration than for axonal/neuronal degeneration.

Suggested Citation

  • Carolina Soares & Bruna Bellaver & Pamela C. L. Ferreira & Guilherme Povala & Cristiano Schaffer Aguzzoli & João Pedro Ferrari-Souza & Hussein Zalzale & Firoza Z. Lussier & Francieli Rohden & Sarah Ab, 2025. "CSF total tau as a proxy of synaptic degeneration," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63545-5
    DOI: 10.1038/s41467-025-63545-5
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    References listed on IDEAS

    as
    1. Akaike, Hirotugu, 1981. "Likelihood of a model and information criteria," Journal of Econometrics, Elsevier, vol. 16(1), pages 3-14, May.
    2. Lujia Zhou & Joseph McInnes & Keimpe Wierda & Matthew Holt & Abigail G. Herrmann & Rosemary J. Jackson & Yu-Chun Wang & Jef Swerts & Jelle Beyens & Katarzyna Miskiewicz & Sven Vilain & Ilse Dewachter , 2017. "Tau association with synaptic vesicles causes presynaptic dysfunction," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
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