To address these open questions, the major aims of the current combined tau-PET and resting-state fMRI study were to assess whether: (1) younger age is associated with stronger tau pathology in globally connected hub regions compared to non-hubs in patients with symptomatic AD; (2) whether tau pathology in hub regions is associated with accelerated subsequent tau spreading and; (3) whether the association between younger age and faster tau accumulation rates in symptomatic AD3 is mediated by stronger tau pathology in globally connected hub regions. Here, MAPT is linked to Alzheimer disease 3.