The amyloidogenic pathway, long regarded as central to AD pathology, involves the initial cleavage of APP by β-site APP-cleaving enzyme 1 (BACE1), generating a membrane-bound C-terminal fragment (C99) and soluble APPβ (sAPPβ), a fragment that lacks the neuroprotective properties of its non-amyloidogenic counterpart (sAPPα) (see Figure 1) [11,14,15]. The gene discussed is APP; the disease is Alzheimer disease.