APP and Alzheimer disease: Most of the AD mouse models which harbor human APP mutation(s) and exhibit early-onset epileptiform activity and seizure susceptibility have increased intraneuronal human APP and Aβ prior to extracellular Aβ deposition and amyloid plaque formation (Oddo et al., 2003a,b; Billings et al., 2005; Lithner et al., 2011; Stargardt et al., 2015).