Interesting new information is provided by a recent study suggesting that during embryonic development TAG1 binds APP. As a result, levels of the C-terminal intracellular domain of APP, namely, AICD, are upregulated in a γ-secretase-dependent manner, leading to modulation of neurogenesis (Ma et al., 2008). However, information concerning the role of AICD in regulation of adult neurogenesis is largely unknown. Recent studies also suggest that PS1/γ-secretase processing of APP regulates EGFR (Zhang et al., 2007; Li et al., 2007; Repetto et al., 2007). PS1/γ-secretase cleavage of APP results in the generation of AICD, which directly binds to EGFR promoter and regulates EGFR gene expression (Zhang et al., 2007). Therefore, FAD alterations in APP and PS1 processing and/or function may affect EGFR expression and function. Reduced PS1/γ-secretase activity is inversely correlated with EGFR levels in fibroblasts and induces skin tumors (Li et al., 2007). These studies suggest that PS1/γ-secretase plays a role of tumor suppressor in fibroblasts. In that regard, PS1 is implicated as a negative regulator of the Wnt/β-catenin signaling pathway (Xia et al., 2001). Following its cleavage, PS1CTF/NTF forms
