Since animal work has also demonstrated the activity-dependent nature of tau accumulation and spread,52,58 we hypothesized that the aforementioned hyperconnectivity effect would be most prominent in the anterior MTL—and the PRC in particular—because this region includes the transentorhinal cortex, the earliest locus of tau pathology in Alzheimer’s disease.12,14,17,21,59 Furthermore, because rising tau is associated with synapse loss, cell death and circuit breakdown,60–62 we predicted that symptomatic stages of Alzheimer’s disease would be characterized by reduced, not excessive, FC levels. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.