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Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease

Author

Listed:
  • Fernando Gonzalez-Ortiz

    (the Sahlgrenska Academy at the University of Gothenburg
    Sahlgrenska University Hospital)

  • Bjørn-Eivind Kirsebom

    (University Hospital of North Norway
    The Arctic University of Norway
    University of Oslo)

  • José Contador

    (Pasqual Maragall Foundation
    Hospital del Mar Research Institute
    Hospital del Mar)

  • Jordan E. Tanley

    (Wake Forest University School of Medicine)

  • Per Selnes

    (Akershus University Hospital)

  • Berglind Gísladóttir

    (Akershus University Hospital)

  • Lene Pålhaugen

    (Akershus University Hospital)

  • Mathilde Suhr Hemminghyth

    (Haugesund Hospital
    Haugesund Hospital
    University of Bergen)

  • Jonas Jarholm

    (Akershus University Hospital)

  • Ragnhild Skogseth

    (Haraldsplass Deaconess Hospital
    University of Bergen)

  • Geir Bråthen

    (University Hospital of Trondheim
    Norwegian University of Science and Technology)

  • Gøril Grøndtvedt

    (University Hospital of Trondheim
    Norwegian University of Science and Technology)

  • Atle Bjørnerud

    (University of Oslo
    Oslo University hospital
    University of Oslo)

  • Sandra Tecelao

    (Akershus University Hospital)

  • Knut Waterloo

    (University Hospital of North Norway
    The Arctic University of Norway)

  • Dag Aarsland

    (Psychology and Neuroscience King’s College London
    Centre for Age-Related Diseases, University Hospital Stavanger)

  • Aida Fernández-Lebrero

    (Pasqual Maragall Foundation
    Hospital del Mar Research Institute
    Hospital del Mar
    Universitat Pompeu Fabra)

  • Greta García-Escobar

    (Hospital del Mar Research Institute
    ERA-Net on Cardiovascular Diseases (ERA-CVD) consortium)

  • Irene Navalpotro-Gómez

    (Pasqual Maragall Foundation
    Hospital del Mar Research Institute
    Hospital del Mar
    ERA-Net on Cardiovascular Diseases (ERA-CVD) consortium)

  • Michael Turton

    (Bioventix Plc)

  • Agnes Hesthamar

    (the Sahlgrenska Academy at the University of Gothenburg)

  • Przemyslaw R. Kac

    (the Sahlgrenska Academy at the University of Gothenburg)

  • Johanna Nilsson

    (the Sahlgrenska Academy at the University of Gothenburg)

  • Jose Luchsinger

    (Wake Forest University School of Medicine)

  • Kathleen M. Hayden

    (Wake Forest University School of Medicine)

  • Peter Harrison

    (Bioventix Plc)

  • Albert Puig-Pijoan

    (Pasqual Maragall Foundation
    Hospital del Mar Research Institute
    ERA-Net on Cardiovascular Diseases (ERA-CVD) consortium
    Universitat Autònoma de Barcelona)

  • Henrik Zetterberg

    (the Sahlgrenska Academy at the University of Gothenburg
    Sahlgrenska University Hospital
    Queen Square
    UK Dementia Research Institute at UCL)

  • Timothy M. Hughes

    (Wake Forest University School of Medicine)

  • Marc Suárez-Calvet

    (Pasqual Maragall Foundation
    Hospital del Mar Research Institute
    Hospital del Mar
    Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES))

  • Thomas K. Karikari

    (the Sahlgrenska Academy at the University of Gothenburg
    University of Pittsburgh)

  • Tormod Fladby

    (University of Oslo
    Akershus University Hospital)

  • Kaj Blennow

    (the Sahlgrenska Academy at the University of Gothenburg
    Sahlgrenska University Hospital)

Abstract

Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer’s disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ (“A”) and neurodegeneration (“N”) abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies.

Suggested Citation

  • Fernando Gonzalez-Ortiz & Bjørn-Eivind Kirsebom & José Contador & Jordan E. Tanley & Per Selnes & Berglind Gísladóttir & Lene Pålhaugen & Mathilde Suhr Hemminghyth & Jonas Jarholm & Ragnhild Skogseth , 2024. "Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47286-5
    DOI: 10.1038/s41467-024-47286-5
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    References listed on IDEAS

    as
    1. Nicholas J. Ashton & Shorena Janelidze & Ahmad Al Khleifat & Antoine Leuzy & Emma L. van der Ende & Thomas K. Karikari & Andrea L. Benedet & Tharick A. Pascoal & Alberto Lleó & Lucilla Parnetti & Dani, 2021. "A multicentre validation study of the diagnostic value of plasma neurofilament light," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

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