the compensatory effects of APLP1 and APLP2 diminish with age, an explanation frequently invoked when the mild phenotype of the APP-deficient mice was first described. Although no compensatory changes in APLP1 or APLP2 expression were detected in 14 weeks old APP−/− mice (Zheng et al., 1995), it is not clear whether there is a reduction in expression of the APP orthologs with age. In this regard, a parallel study in APLP2 failed to detect any changes in dendritic morphology or spine density in either young or old animals (Midthune et al., 2012), a situation that is quite different from what we saw in the present study. Consequently, it will be interesting to determine whether there is an age-associated reduction in the expression or levels of APLP1 or APLP2.
