Amyloid and tau accumulate across distinct spatial networks and are differentially associated with brain connectivity

  1. Joana B Pereira  Is a corresponding author
  2. Rik Ossenkoppele
  3. Sebastian Palmqvist
  4. Tor Olof Strandberg
  5. Ruben Smith
  6. Eric Westman
  7. Oskar Hansson  Is a corresponding author
  1. Karolinska Institute, Sweden
  2. VU University Medical Center, Netherlands
  3. Lund University, Sweden

Abstract

The abnormal accumulation of amyloid-β and tau targets specific spatial networks in Alzheimer's disease. However, the relationship between these networks across different disease stages and their association with brain connectivity has not been explored. In this study, we applied a joint independent component analysis to 18F- Flutemetamol (amyloid-β) and 18F-Flortaucipir (tau) PET images to identify amyloid-β and tau networks across different stages of Alzheimer's disease. We then assessed whether these patterns were associated with resting-state functional networks and white matter tracts. Our analyses revealed nine patterns that were linked across tau and amyloid-β data. The amyloid-b and tau patterns showed a fair to moderate overlap with distinct functional networks but only tau was associated with white matter integrity loss and multiple cognitive functions. These findings show that amyloid-b and tau have different spatial affinities, which can be used to understand how they accumulate in the brain and potentially damage the brain's connections.

Data availability

Source data files have been provided for Figures 4 and 5. The source data for the rest of the analyses performed in this study can be requested from Prof. Oskar Hansson (Oskar.Hansson@med.lu.se), after signing a material transfer agreement from Lund University that ensures that the data will only be used for the sole purpose of replicating procedures and results presented in the article and as long as data transfer is in agreement with EU legislation on the general data protection regulation and decisions by the Ethical Review Board of Sweden and Region Skåne.

Article and author information

Author details

  1. Joana B Pereira

    Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
    For correspondence
    joana.pereira@ki.se
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4604-2711
  2. Rik Ossenkoppele

    Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, Netherlands
    Competing interests
    No competing interests declared.
  3. Sebastian Palmqvist

    Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
    Competing interests
    No competing interests declared.
  4. Tor Olof Strandberg

    Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
    Competing interests
    No competing interests declared.
  5. Ruben Smith

    Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
    Competing interests
    No competing interests declared.
  6. Eric Westman

    Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  7. Oskar Hansson

    Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden
    For correspondence
    oskar.hansson@med.lu.se
    Competing interests
    Oskar Hansson, has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio, and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Biogen, Roche, and Fujirebio.

Funding

European Research Council, Swedish Research Council, Swedish Brain Foundation, Startneuro, Swedish Alzheimer Foundation, Knut and Alice Wallenberg foundation, Strategic Research Area Multipark

  • Oskar Hansson

Swedish Research Council, Alzheimerfonden, Swedish Brain Research

  • Joana B Pereira

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study received ethical approval from the Regional Ethical Review Board of Lund University (Dnr 2008-695, 2008-290, 2010-156), the Swedish Medicines and Products Agency (Dnr 151:2012/4552, 5.1-2014-62949), and the Radiation Safety Committee of Skåne University Hospital in Sweden. All participants provided informed consent before being included in the study.

Reviewing Editor

  1. Muireann Irish, University of Sydney, Australia

Publication history

  1. Received: August 4, 2019
  2. Accepted: December 6, 2019
  3. Accepted Manuscript published: December 9, 2019 (version 1)
  4. Version of Record published: December 31, 2019 (version 2)

Copyright

© 2019, Pereira et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Joana B Pereira
  2. Rik Ossenkoppele
  3. Sebastian Palmqvist
  4. Tor Olof Strandberg
  5. Ruben Smith
  6. Eric Westman
  7. Oskar Hansson
(2019)
Amyloid and tau accumulate across distinct spatial networks and are differentially associated with brain connectivity
eLife 8:e50830.
https://doi.org/10.7554/eLife.50830

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