APP and Alzheimer disease: According to amyloid hypothesis, β-site amyloid cleaving enzyme (BACE-1) cleaves amyloid precursor protein (APP) at its extracellular site followed by intra-membrane cleavage by γ-secretase releasing insoluble Aβ peptides (Aβ40 or Aβ42 residues) causing extracellular plaque formation in amyloidogenic pathway of AD.