Based on these data, we show that (1) individual tau-PET deposition patterns are indeed stronger in globally connected hub regions in younger patients with symptomatic AD and associated with earlier symptom onset; (2) that a more hub-like pattern of tau pathology deposition at baseline is associated with accelerated subsequent annual tau accumulation and; (3) that the association between younger age and faster tau accumulation rates in symptomatic AD is mediated by a more hub-like tau-PET pattern thereby driving faster cognitive decline. This evidence concerns the gene MAPT and Alzheimer disease.