APP and familial Alzheimer disease: Extensive experimental efforts over the past decades have identified the role of familial AD (fAD) mutations in early impairments of synaptic transmission and plasticity in hippocampal circuits via Aβ and other cleavage products of Aβ precursor protein (APP) processing (Fogel et al., 2014; Hsia et al., 1999; Li et al., 2009; Rice et al., 2019; Shankar et al., 2008; Wang et al., 2017; Willem et al., 2015).