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 ; Hager, Paul ; Steward, Anna; Dewenter, Anna ; Römer, Sebastian ; Rubinski, Anna; Buerger, Katharina; Janowitz, Daniel; Pichet Binette, Alexa ; Smith, Ruben ; Strandberg, Olof; Carlgren, Niklas Mattsson; Dichgans, Martin ; Hansson, Oskar; Franzmeier, Nicolai (2022): Earlier Alzheimer’s disease onset is associated with tau pathology in brain hub regions and facilitated tau spreading. Nature Communications, 13: 4899. ISSN 2041-1723

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.

• Doc-Type: Article (LMU Hospital)
• Organisational unit (Faculties): 07 Medicine > Medical Center of the University of Munich > Institute for Stroke and Dementia Research (ISD)
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892