APP and Alzheimer disease: The pathophysiology of AD is the formation and accumulation of extracellular amyloid-beta (Aβ), plaques, intracellular neurofibrillary tangles, and a loss of connection among the nerve cells in the brain [3,4,5] Aβ-peptide is generated from a transmembrane protein called the amyloid precursor protein (APP) by the action of a beta secretase-1 enzyme (BACE-1) [6,7].