Assuming that tau spreads trans-synaptically and impairs functional connectivity,19,51 the current finding of a less disrupted avDMN and vDMN connectivity in LPA fits with our recent report that, in a partially overlapping cohort, LPA participants exhibited significantly faster rates of tau-PET uptake accumulation across the cortex than PCA.54 In addition, avDMN and vDMN were the two sub-systems whose connectivity was negatively associated with tau burden in atypical Alzheimer’s disease participants. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.