ADORA2A and Alzheimer disease: These mechanistic links are in agreement with the observed upregulation of A2AR in synapses as well as in total membranes of the hippocampus during the presymptomatic phase of AD; however, future work is required to unveil the relative contribution of these different mechanism(s) operated by A2AR to control hippocampal hyperexcitability present during the presymptomatic phase of AD.