The “amyloid cascade hypothesis” of Alzheimer's disease (AD) proposes disease is caused by accumulation of the β-amyloid (Aβ) peptide (typically up to 42 residues in length) that is proteolytically derived from the amyloid precursor protein (APP; Hardy and Higgins, 1992; Masters and Selkoe, 2012). This evidence concerns the gene APP and early-onset autosomal dominant Alzheimer disease.