An important finding from the in vivo studies was that the changes in neuronal morphology in the older group of APP-deficient mice were absent in the young mice. We did not anticipate these age-associated alterations given the observations from cultured hippocampal neurons (Fig. 1). Specifically, the reduction in apical dendritic length, dendritic arborization, and spine density were only present in the older cohort of animals (Table 1). Our findings therefore suggest that APP plays a specific role in the maintenance of dendritic complexity and spine numbers that manifest itself during the aging process. The number of dendritic spines is generally believed to be an end result of a balance between spine formation and spine elimination. Because spine density was unchanged in the younger animals and because addition of new stable dendritic spines is thought to be infrequent in adult mice (Alvarez and Sabatini, 2007), we hypothesize that the reduction in spine density in the older animals is the result of increased spine elimination. In this context, it is noteworthy that the reduction in dendritic complexity is of greater magnitude than
