The marked reduction in dendritic spine numbers in cultured hippocampal neurons from APP−/− mice was surprising as this alteration has, to our knowledge, not been reported before. In fact, autaptic neurons from APP−/− mice showed an increase in synaptophysin-immunopositive puncta (Priller et al., 2006). We also observed a decrease in dendritic branching in APP−/− neurons in primary cultures (Fig. 1). Thus, we next evaluated the dendritic and spine morphology in APP−/− mice in vivo in more detail. Brain slices of five to six animals in each group (APP+/− and APP−/−) from two ages were examined (2-4 months-old and 12-15 months-old). We first examined each Lucifer Yellow-injected neuron for various morphometric parameters (i.e. dendritic length and complexity) by performing 3-dimensional tracing of each neuron. Sholl analyses showed that CA1 neurons in old APP−/− mice (~13 months old) are significantly less complex in apical arbors than in control (APP+/−) mice (Fig. 2A, B). Apical dendritic length was also shorter in old APP−/− mice compared to APP+/− mice, but no significant changes were seen in basal dendritic length (Table 1). Further analysis showed
