APP and Alzheimer disease: Since plasma levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and macrophage inflammatory protein (MIP)-2 significantly increased in 6-month-old APP/PS1 mice compared with wild-type control mice [42], we propose the hypothesis by which systemic inflammatory signaling may induce AQP5 downregulation in submandibular glands in these mouse models of AD.