APP and Alzheimer disease: Sequential cleavage of APP by the β-secretase, β-site APP cleaving enzyme 1 (BACE1) and the γ-secretase complex (presenilin 1, presenilin 2, nicastrin, anterior pharynx defective 1 homolog A, and other uncharacterized subunits) releases sAPPβ, the APP intracellular domain (AICD) and amyloidogenic Aβ peptide (Figure 1C), the major component of extracellular plaques found in AD (Thinakaran and Koo, 2008).