Thus, it was shown that the activity of these A2AR—with increased density in the presymptomatic period of AD that is maintained throughout the phenotypic expression of synaptic and memory deficits characteristic of early AD—is required both for the adaptive hyperexcitability before memory deficits as well as for the expression of synaptic and memory deficits present at the onset of symptomatic AD. The gene discussed is ADORA2A; the disease is Alzheimer disease.