IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32592-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32592-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32592-7?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. 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.
    2. 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.
    3. 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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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.

    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. Nicolai Franzmeier & Matthias Brendel & Leonie Beyer & Luna Slemann & Gabor G. Kovacs & Thomas Arzberger & Carolin Kurz & Gesine Respondek & Milica J. Lukic & Davina Biel & Anna Rubinski & Lukas Front, 2022. "Tau deposition patterns are associated with functional connectivity in primary tauopathies," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Julie Ottoy & Min Su Kang & Jazlynn Xiu Min Tan & Lyndon Boone & Reinder Vos de Wael & Bo-yong Park & Gleb Bezgin & Firoza Z. Lussier & Tharick A. Pascoal & Nesrine Rahmouni & Jenna Stevenson & Jaime , 2024. "Tau follows principal axes of functional and structural brain organization in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. 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.
    4. Sadhana Ravikumar & Amanda E. Denning & Sydney Lim & Eunice Chung & Niyousha Sadeghpour & Ranjit Ittyerah & Laura E. M. Wisse & Sandhitsu R. Das & Long Xie & John L. Robinson & Theresa Schuck & Edward, 2024. "Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. 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.

    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:13:y:2022:i:1:d:10.1038_s41467-022-32592-7. 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.