APP and Alzheimer disease: Elevated Aβ levels in AD patients (Chen et al., 2014; Klunk et al., 2009; Villemagne et al., 2011, 2013), genetic determinants of AD that affect APP processing (Hardy and Higgins, 1992), and the neurotoxicity of Aβ plaques (Selkoe, 1991) are factors that all support the amyloid cascade hypothesis.