APP and Alzheimer disease: It has been proposed that the accumulation and deposition of “synaptotoxic” amyloid-β (Aβ) peptides, which are produced by sequential cleavage of APP by β- and γ-secretases (Lichtenthaler et al., 2011), are responsible for synapse loss, which is regarded as the significant structural hallmark of cognitive decline in Alzheimer’s disease (AD).