Given the importance of meticulous Arc regulation for the proper functioning of synaptic machinery [33–36] and the role that activity-dependent Arc expression plays in memory-related physiology through AMPAR endocytosis [35], structural plasticity [37] and synaptic tagging [38], our data suggest that mechanisms not linked to experience-dependent immediate early genes are behind behavioral phenotypes in rTg4510 mice and cognitive impairment in AD. The gene discussed is ARC; the disease is Alzheimer disease.