APP and Alzheimer disease: Although abundant evidence has implicated the accumulation of β-amyloid peptides (Aβ) in this process, it is worth noting that Aβ is generated through activity-dependent processing of the amyloid precursor protein (APP; Haass et al., 2012), highlighting the need for understanding AD pathogenesis in the context of APP physiologic function, particularly the establishment and maintenance of neuronal circuits and synaptic connectivity.