In conclusion, our data defines a role of APP in maintenance of dendritic structure and synapse formation and function. We demonstrated that the loss of APP results in alterations in dendritic length and complexity, and spine density in old APP−/− mice and in cultured hippocampal neurons. These changes were correlated with impairment in synaptic function as indicated by the decrease in LTP. Importantly, our data suggests that this physiological role of APP is age-dependent, seen only in aged animals. While the complete cellular functions of full-length APP and its proteolytic cleavage fragments are still incompletely characterized, it is possible that their role in synapse maintenance may, in part, underlie the cognitive deficits and neuronal pathology observed in AD.
