APP and Alzheimer disease: Among APP-overexpressing mouse models, the 3xTg-AD strain exhibited increased PDE4B and PDE4D protein levels in hippocampus and PFC, which were decreased by rolipram [22], and the APPswe/PSEN1dE9 strain exhibited increased PDE4B and PDE4D protein levels in cerebral cortex, which were decreased by roflumilast [24].