The mechanisms that cause the profound degeneration of cortical neurons in AD are not known. Arguments have been presented suggesting that AD-related neurodegeneration is apoptosis (130) and is not apoptosis (131,132). Among many others, the possible mechanisms for neuronal death in AD may involve presynaptic afferent defects (133,134), postsynaptic NMDA receptor abnormalities (135), and altered processing of APP and presenilin proteins. APP is the source of amyloid-s protein (As). The amyloid hypothesis of AD is based on the premise that generation of As by cleavage of APP is a critical pathogenic mechanism. Overexpression and intracellular accumulation of APP activates caspase-3 (136).