The familial AD mouse models which carry human APP mutation(s) and display early-onset epileptiform activity and seizure susceptibility have increased expression of intraneuronal human APP and Aβ before extracellular Aβ deposition and amyloid plaque formation (Oddo et al., 2003a,b; Billings et al., 2005; Lithner et al., 2011; Stargardt et al., 2015). Here, APP is linked to Alzheimer disease.