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

Frontzkowski, Lukas ; Ewers, Michael ; Brendel, Matthias ; Biel, Davina ; Ossenkoppele, Rik LU ; Hager, Paul ; Steward, Anna ; Dewenter, Anna ; Römer, Sebastian and Rubinski, Anna , et al. (2022) In Nature Communications 13(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
13
issue
1
article number
4899
publisher
Nature Publishing Group
external identifiers
  • scopus:85136686870
  • pmid:35987901
ISSN
2041-1723
DOI
10.1038/s41467-022-32592-7
language
English
LU publication?
yes
id
ec6f5ffc-bfc7-4677-a1db-279ffa667b1a
date added to LUP
2022-10-17 08:36:10
date last changed
2024-06-13 09:52:48
@article{ec6f5ffc-bfc7-4677-a1db-279ffa667b1a,
  abstract     = {{<p>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.</p>}},
  author       = {{Frontzkowski, Lukas and Ewers, Michael and Brendel, Matthias and Biel, Davina and Ossenkoppele, Rik and Hager, Paul and Steward, Anna and Dewenter, Anna and Römer, Sebastian and Rubinski, Anna and Buerger, Katharina and Janowitz, Daniel and Binette, Alexa Pichet and Smith, Ruben and Strandberg, Olof and Carlgren, Niklas Mattsson and Dichgans, Martin and Hansson, Oskar and Franzmeier, Nicolai}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Earlier Alzheimer’s disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading}},
  url          = {{http://dx.doi.org/10.1038/s41467-022-32592-7}},
  doi          = {{10.1038/s41467-022-32592-7}},
  volume       = {{13}},
  year         = {{2022}},
}