and in regulation of neurogenesis in the adult SVZ (Maurer et al., 2007), raising the possibility that alterations in GSK3 kinase activity in the SVZ and SGL microenvironments underlie alterations in tau phosphorylation in these neurogenic niches of adult mice. Wen and colleagues show an interplay between cyclin-dependent kinase 5 (cdk5), previously shown to be central for tau phosphorylation (Noble et al., 2003) and GSK3β in mice overexpressing p25. While cdk5 activity increases APP processing, GSK3β activity induces tau phosphorylation. Interestingly, inhibition of cdk5 activates GSK3β activity (Wen et al., 2008a). Finally, transcriptional regulation of β-secretase by cdk5 was also shown to lead to enhanced amyloidogenic processing of APP (Wen et al., 2008b). Therefore, these kinases may function as a critical focal point for processes that mediate both neurogenesis and AD.
