mouse models, both knock-in (4 with truncated alleles and 2 with C-terminal point mutation alleles) and knock-out (2 KO and 2 conditional), that suffer from various defects and abnormalities (reviewed in (Guo et al., 2011). One APP KO mouse generated by Zheng et al. (1995) shows many deficits in locomotor activity and forelimb grip strength, as well as impairments in learning and memory associated with deficits in long-term potentiation (LTP) (Ring et al., 2007). In fact alterations in synaptic structure and function are some of the most consistent findings of in vitro studies using neurons from either APP-deficient mice or from RNAi-mediated knockdown approaches (Herard et al., 2006; Hoe et al., 2009; Lee et al., 2010; Seabrook et al., 1999; Zheng et al., 1995). This APP mouse model also shows changes in dendritic arborization (Seabrook et al., 1999) and synapse numbers (Lee et al., 2010), although the latter finding was not supported by another study (Phinney et al., 1999). In contrast, a study using autaptic hippocampal cultures derived from a different APP KO mouse line showed an increase in synaptophysin-immunoreactive puncta and miniature synaptic currents (Priller et al., 2006). These conflicting results are compounded by APLP1 and APLP2, which likely
