APP and Cognitive impairment: Notably, Hippo activation is associated with cognitive deficits and neuronal loss, as HDAC3 knockdown in the APP/PS1 hippocampus both reverses pathological activation of Hippo signaling and protects against cognitive deficits and neuronal loss [22], implying an upstream role for HDAC3 in Hippo pathway regulation, though whether the cognitive improvements directly resulted from inactivation of Hippo signaling was not fully explored in the study.