APOE and amyloidosis: It has also been shown in a recent study, however, that neural hyperactivity can also occur in APOE-ɛ4 mouse models in the absence of overt amyloid or tau pathology (Nuriel et al., 2017) via a mechanism in which APOE-ɛ4 leads to an overall decrease in inhibition caused by a reduced responsiveness of excitatory neurons to GABAergic input.