ADORA2A and Alzheimer disease: To determine the impact of early A2AR neuronal upregulation, as seen in the aged and AD human brain,21 on the pathophysiological development of the APP/PS1 amyloid mouse model, we took advantage of a conditional strain that we developed recently.27 This model, carrying the mouse A2AR transgene under the control of a Tet-responsive element (TRE-A2A strain), was crossed with APP/PS1 mice (Fig. 1A).