APP and Alzheimer disease: Extracellular Aβ deposition (including Aβ40 and Aβ42), produced by protease cleavage of the type I transmembrane amyloid precursor protein (APP), can cause secondary pathological changes such as hyperphosphorylation of tau (p-tau), neuroinflammation, oxidative stress, and neurite degeneration, eventually leading to AD (Hardy and Selkoe, 2002).