APP and Alzheimer disease: Roughly 15 years (2, 3) prior to the onset of symptoms, AD is thought to begin with the dysregulation of metabolic processes that include elevated production of Aβ peptides—a quintet of overlapping peptides (36–42-mers) proteolytically clipped by β- and γ-secretase from a trans-membrane segment of the amyloid precursor protein (APP) (4).