APP and Alzheimer disease: The major hallmarks of AD are soluble toxic amyloid-β (Aβ) peptide oligomers [2], which are proteolytic fragments of the amyloid precursor protein (APP) cleavage by β-secretases and γ-secretases [3], neurofibrillary tangles (NFTs) primarily composed of hyperphosphorylated tau proteins [4], selective basal forebrain cholinergic neuron (BFCN) degeneration and brain atrophy [5].