APP and Alzheimer disease: In AD, amyloid β-peptides (Aβ) formed by proteolytic cleavage of the amyloid precursor protein (APP) by secretases aggregate into extracellular amyloid plaques, and hyperphosphorylated tau accumulates intracellularly to form neurofibrillary tangles (NFTs; Masters et al., 1985; Grundke-Iqbal et al., 1986).