Tau covariance patterns in Alzheimer's disease patients match intrinsic connectivity networks in the healthy brain

According to the network model of neurodegeneration, the spread of pathogenic proteins occurs selectively along connected brain regions. We tested in vivo whether the distribution of filamentous tau (measured with [ F]flortaucipir-PET), fibrillar amyloid-β ([ C]PIB-PET) and glucose hypometabolism ([ F]FDG-PET) follows the intrinsic functional organization of the healthy brain. We included 63 patients with Alzheimer's disease (AD; 30 male, 63 ± 8 years) who underwent [ F]flortaucipir, [ C]PIB and [ F]FDG PET, and 1000 young adults (427 male, 21 ± 3 years) who underwent task-free fMRI. We selected six predefined disease epicenters as seeds for whole-brain voxelwise covariance analyses to compare correlated patterns of tracer uptake across AD patients against fMRI intrinsic connectivity patterns in young adults. We found a striking convergence between [ F]flortaucipir covariance patterns and intrinsic connectivity maps (range Spearman rho's: 0.32-0.78, p