Chunk #33 — Converging Pathways Implicated in Neurogenesis and AD Pathology — Wnt, reelin and the low-density lipoprotein receptor family in neurogenesis and AD
Numerous studies during the last 10 years established that LDLR linked cellular signaling pathways modulate AD pathology [For review see (Qiu et al., 2006)]. Reelin and its homolog F-spondin are recognized by the very-low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor-2 (apoE-R2), two members of the LDLR family. Mice lacking Reelin, double-knockouts lacking VLDLR and ApoER2, and mice lacking disabled-1 (Dab1) display increased levels of phosphorylated tau. It was suggested that the reelin-ApoE receptor complex initiates a signaling cascade that regulates phosphorylation of tau by GSK3 (Ohkubo et al., 2003). F-spondin and recently reelin have been shown to regulate APP processing through their interaction with APP and ApoER-2 (Hoe and Rebeck, 2008; Hoe et al., 2009; Hoe et al., 2005b). ApoER-2 has also been shown to be neuroprotective during aging (Beffert et al., 2006), and F-spondin was reported to protect against Aβ toxicity (Cheng et al., 2009). Finally, reelin expression has recently been shown to be downregulated in APP transgenic mice and in AD (Chin et al., 2007). Other LDLR family members including LRP1, LRP1B, and LR11/sorLA have also
