INS and Alzheimer disease: Moreover, the primary location of IRs at the synapses, where their signaling may contribute to synaptic remodeling (together with a role on memory formation under normal metabolic conditions) (101), and the long known modulatory role for insulin against deleterious Aβ synaptic accumulation and effects (42), further suggest that insulin administration (without hypoglycemic episodes) or, even better, the pharmacologic restoration of brain insulin sensitivity and action could be one of the best promising therapeutic approaches against AD.