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Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease

Author

Listed:
  • Nicolai Franzmeier

    (Ludwig-Maximilians-Universitat LMU)

  • Julia Neitzel

    (Ludwig-Maximilians-Universitat LMU)

  • Anna Rubinski

    (Ludwig-Maximilians-Universitat LMU)

  • Ruben Smith

    (Skane University Hospital
    Lund University)

  • Olof Strandberg

    (Lund University)

  • Rik Ossenkoppele

    (Lund University
    Vrije Universiteit Amsterdam, Amsterdam UMC)

  • Oskar Hansson

    (Lund University
    Skane University Hospital)

  • Michael Ewers

    (Ludwig-Maximilians-Universitat LMU)

Abstract

In Alzheimer’s diseases (AD), tau pathology is strongly associated with cognitive decline. Preclinical evidence suggests that tau spreads across connected neurons in an activity-dependent manner. Supporting this, cross-sectional AD studies show that tau deposition patterns resemble functional brain networks. However, whether higher functional connectivity is associated with higher rates of tau accumulation is unclear. Here, we combine resting-state fMRI with longitudinal tau-PET in two independent samples including 53 (ADNI) and 41 (BioFINDER) amyloid-biomarker defined AD subjects and 28 (ADNI) vs. 16 (BioFINDER) amyloid-negative healthy controls. In both samples, AD subjects show faster tau accumulation than controls. Second, in AD, higher fMRI-assessed connectivity between 400 regions of interest (ROIs) is associated with correlated tau-PET accumulation in corresponding ROIs. Third, we show that a model including baseline connectivity and tau-PET is associated with future tau-PET accumulation. Together, connectivity is associated with tau spread in AD, supporting the view of transneuronal tau propagation.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14159-1
    DOI: 10.1038/s41467-019-14159-1
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    Cited by:

    1. 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.
    2. 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.
    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. 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.
    5. 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.
    6. 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.

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