APP and Alzheimer disease: Senile plaques composed of extracellular amyloid β peptide (Aβ) and neurofibrillary tangles (NFT), which are the aggregates of intracellular hyperphosphorylated tau protein, are hallmarks of the AD brain.1 Aβ deposition and NFT formation in the cortical region of the brain begin appearing 25–30 years and 15 years, respectively, before the clinical onset of AD (Fig. 1a).2 Aβ is generated proteolytically from amyloid precursor protein (APP) to subsequently form oligomeric Aβ, which aggregates into senile plaques.