In Drosophila, Notch mutations lost a lateral signaling ability and produced a neurogenic phenotype, where cells destined to become epidermis switch fate and give rise to neural tissue (Artavanis-Tsakonas et al. 1995; Lewis 1998). Therefore, when Notch signaling was disrupted, too many neurons were generated. Notch attracted further interest because sel12, which appears to facilitate the reception of signaling mediated by lin-12 (C. elegans Notch), was identified by screening for a suppressor of lin-12 gain-of-function mutation (Levitan and Greenwald 1995). Since sel-12 is thought to be a counterpart of human presenilin (PS), which is a catalytic component of -secretase and has been implicated in Alzheimer’s disease (AD), it was thought that the Notch signaling pathway might have a close relation with AD. Thus, many scientists have investigated the relationship between Notch signaling and AD. As we focused below, it has become clear that the Notch signaling pathway is controlled by -secretase-mediated proteolysis.