A role for APP in the development of astrocyte morphological complexity

The amyloid precursor protein (APP), whose proteolytic cleavage gives rise to amyloid-{beta} peptide, has been extensively studied for its role in Alzheimers disease, but its physiological function remains less understood. In neurons, APP and its two homologs, the amyloid precursor-like protein 1 (APLP1) and 2 (APLP2), are present in the synaptic compartment and promote synaptogenesis. Over recent years, astrocytes, an abundant glial cell in the brain, have attracted much attention for their role in regulating synapse formation and function. Although APP is also found in astrocytes, its role in these cells remains largely unexplored. Here we have sought to investigate the expression and function of APP in rodent astrocytes in vitro and in vivo. We find that APP along with its family members, APLP1 and APLP2, are expressed in astrocytes in vitro and in vivo. In primary hippocampal cultures, shRNA-mediated knockdown of astrocytic APP, APLP1 or APLP2 compromises astrocyte morphological elaboration to varying degrees. We have then focused on APP to characterize its role in astrocyte development in the intact brain. We show that astrocytic APP shapes the morphological complexity of astrocyte processes in vivo and may also modulate postsynaptic assembly. Our results highlight a role of astrocytic APP and possibly of APLPs that could potentially impact neuronal functions.