Recent studies suggest that in young APPswe/PS1ΔE9 mice, neural progenitor cell proliferation and early differentiation is impaired in the SVZ, a neurogenic area exhibiting low steady state levels of Aβ but a dramatic increase in tau phosphorylation. Importantly, increase in PHF-1-immunoreactive phosphorylated tau is detected as early as 2 months of age (Demars et al., 2009). The known function-associated phosphorylation sites of tau are reportedly on serine and threonine, suggesting a role for serine and threonine kinases and phosphatases in AD. There are more than ten serine/threonine protein kinases that have been shown to phosphorylate tau in vitro. According to the motif-specificity, these kinases can be divided into two major groups, i.e., the proline-directed protein kinases (PDPKs) and nonproline- directed protein kinases (NPDPKs). Among these kinases, GSK-3β is among the most implicated in the abnormal hyperphosphorylation of tau in AD brains. As discussed above, glycogen synthase kinase 3 (GSK3) is a component of the Wnt signaling pathway, that plays a major role in adult neurogenesis (Lie et al., 2005), microtubule dynamics and fast axonal transport (Frame et al., 2001; Morfini
