APP and Alzheimer disease: Extracellular amyloid plaques formed by amyloid precursor protein(APP) and intracellular neurofibrillary tangles resulting from hyperphosphorylatedtau protein in the cortical and hippocampal regions are the key pathologicalhallmarks of AD.8 The catalytic proteasesinvolved in APP proteolysis include α-, β-, and γ-secretases.This process forms the basis of the amyloidogenic pathway with β-and γ-secretase and the nonamyloidogenic pathway with α-secretase,generating insoluble and soluble neurotic amyloid plaques, respectively(Figure 2).9