MAPT and tauopathy: Given that the EC is one of the first regions to be affected by overt tauopathy in the earliest stages of human AD44, our data showing that APOE4 is associated with neuronal hyperactivity in this region could indicate that APOE4 may accelerate the accumulation and propagation of Aβ or tau (or both), thereby accelerating the onset of AD in APOE4 carriers.