The neuroprotective effect of caffeine in different animal models of neuropsychiatric disorders, including AD [9,10], has been linked to the ability of caffeine to normalize synaptic plasticity via A2AR (reviewed in [15]), since the overactivation of hippocampal A2AR is sufficient to trigger memory impairment [16,17,18] and is critically necessary for the emergence of synaptic and memory deficits in different animal models of early AD [19,20,21,22]. Here, ADORA2A is linked to Alzheimer disease.