marked reduction in dendritic length and branching were seen only in older (12-14 months) but not in young (2-4 months) APP−/− animals. Furthermore, consistent with changes in altered neuronal morphology in older animals, synaptic plasticity as measured by LTP was also impaired only in older but not young APP−/− mice, the former in agreement with previous reports. The marked reduction dendritic spine densities in vitro in APP−/− neurons and the restoration of this loss by conditioned medium from wild type neurons suggests that secreted sAPP, in particular sAPPα rather than sAPPβ, plays an important in maintaining spines. Taken together, these results indicate that deficiency in APP alone results in gradual reduction in dendritic structure and synaptic function during aging. This suggests a physiological role of APP in the maintenance rather than in the formation of dendritic spine structure.
