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

Lukas Frontzkowski, Michael Ewers, Matthias Brendel, Davina Biel, Rik Ossenkoppele, Paul Hager, Anna Steward, Anna Dewenter, Sebastian Römer, Anna Rubinski, Katharina Buerger, Daniel Janowitz, Alexa Pichet Binette, Ruben Smith, Olof Strandberg, Niklas Mattsson Carlgren, Martin Dichgans, Oskar Hansson and Nicolai Franzmeier ()
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Lukas Frontzkowski: University Hospital, LMU Munich
Michael Ewers: University Hospital, LMU Munich
Matthias Brendel: University Hospital, LMU Munich
Davina Biel: University Hospital, LMU Munich
Rik Ossenkoppele: Lund University
Paul Hager: University Hospital, LMU Munich
Anna Steward: University Hospital, LMU Munich
Anna Dewenter: University Hospital, LMU Munich
Sebastian Römer: University Hospital, LMU Munich
Anna Rubinski: University Hospital, LMU Munich
Katharina Buerger: University Hospital, LMU Munich
Daniel Janowitz: University Hospital, LMU Munich
Alexa Pichet Binette: Lund University
Ruben Smith: Lund University
Olof Strandberg: Lund University
Niklas Mattsson Carlgren: Lund University
Martin Dichgans: University Hospital, LMU Munich
Oskar Hansson: Lund University
Nicolai Franzmeier: University Hospital, LMU Munich

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32592-7

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DOI: 10.1038/s41467-022-32592-7

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