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Earlier Alzheimer’s disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading

Author

Listed:
  • Lukas Frontzkowski

    (University Hospital, LMU Munich)

  • Michael Ewers

    (University Hospital, LMU Munich
    German Center for Neurodegenerative Diseases (DZNE))

  • Matthias Brendel

    (University Hospital, LMU Munich
    Munich Cluster for Systems Neurology (SyNergy))

  • Davina Biel

    (University Hospital, LMU Munich)

  • Rik Ossenkoppele

    (Lund University
    Vrije Universiteit Amsterdam, Amsterdam UMC)

  • Paul Hager

    (University Hospital, LMU Munich)

  • Anna Steward

    (University Hospital, LMU Munich)

  • Anna Dewenter

    (University Hospital, LMU Munich)

  • Sebastian Römer

    (University Hospital, LMU Munich
    University Hospital, LMU Munich)

  • Anna Rubinski

    (University Hospital, LMU Munich)

  • Katharina Buerger

    (University Hospital, LMU Munich
    German Center for Neurodegenerative Diseases (DZNE))

  • Daniel Janowitz

    (University Hospital, LMU Munich)

  • Alexa Pichet Binette

    (Lund University)

  • Ruben Smith

    (Lund University
    Skåne University Hospital)

  • Olof Strandberg

    (Lund University)

  • Niklas Mattsson Carlgren

    (Lund University
    Skåne University Hospital)

  • Martin Dichgans

    (University Hospital, LMU Munich
    German Center for Neurodegenerative Diseases (DZNE)
    Munich Cluster for Systems Neurology (SyNergy))

  • Oskar Hansson

    (Lund University
    Skåne University Hospital)

  • Nicolai Franzmeier

    (University Hospital, LMU Munich
    Munich Cluster for Systems Neurology (SyNergy))

Abstract

In Alzheimer’s disease (AD), younger symptom onset is associated with accelerated disease progression and tau spreading, yet the mechanisms underlying faster disease manifestation are unknown. To address this, we combined resting-state fMRI and longitudinal tau-PET in two independent samples of controls and biomarker-confirmed AD patients (ADNI/BioFINDER, n = 240/57). Consistent across both samples, we found that younger symptomatic AD patients showed stronger tau-PET in globally connected fronto-parietal hubs, i.e., regions that are critical for maintaining cognition in AD. Stronger tau-PET in hubs predicted faster subsequent tau accumulation, suggesting that tau in globally connected regions facilitates connectivity-mediated tau spreading. Further, stronger tau-PET in hubs mediated the association between younger age and faster tau accumulation in symptomatic AD patients, which predicted faster cognitive decline. These independently validated findings suggest that younger AD symptom onset is associated with stronger tau pathology in brain hubs, and accelerated tau spreading throughout connected brain regions and cognitive decline.

Suggested Citation

  • Lukas Frontzkowski & Michael Ewers & Matthias Brendel & Davina Biel & Rik Ossenkoppele & Paul Hager & Anna Steward & Anna Dewenter & Sebastian Römer & Anna Rubinski & Katharina Buerger & Daniel Janowi, 2022. "Earlier Alzheimer’s disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32592-7
    DOI: 10.1038/s41467-022-32592-7
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    References listed on IDEAS

    as
    1. Nicolai Franzmeier & Julia Neitzel & Anna Rubinski & Ruben Smith & Olof Strandberg & Rik Ossenkoppele & Oskar Hansson & Michael Ewers, 2020. "Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Nicolai Franzmeier & Anna Rubinski & Julia Neitzel & Michael Ewers, 2019. "The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    3. Jacob W. Vogel & Yasser Iturria-Medina & Olof T. Strandberg & Ruben Smith & Elizabeth Levitis & Alan C. Evans & Oskar Hansson, 2020. "Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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    Cited by:

    1. Nicolai Franzmeier & Amir Dehsarvi & Anna Steward & Davina Biel & Anna Dewenter & Sebastian Niclas Roemer & Fabian Wagner & Mattes Groß & Matthias Brendel & Alexis Moscoso & Prithvi Arunachalam & Kaj , 2024. "Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Sophie E. Mastenbroek & Jacob W. Vogel & Lyduine E. Collij & Geidy E. Serrano & Cécilia Tremblay & Alexandra L. Young & Richard A. Arce & Holly A. Shill & Erika D. Driver-Dunckley & Shyamal H. Mehta &, 2024. "Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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