APP and Alzheimer disease: Since 1992, the etiology and pathogenesis of AD has been explained by the amyloid cascade hypothesis, in which the accumulation of pathogenetic amyloid β (Aβ) protein, derived from APP, induces a vicious cycle that triggers the accumulation of neurofibrillary tangles (NFTs), neuronal cell death, and ultimately dementia (Reitz, 2012).