 The brain requires integral insulin signaling for metabolic homeostasis and neuronal plasticity. Insulin resistance disrupts energy balance and signaling networks needed for a broad range of functions. Impaired insulin signaling in neurons enhances apoptosis, promotes oxidative cell death induced by Abeta1-42, increases secretion of Abeta1-42, blocks removal of extracellular Abeta oligomers and increases plaque loads. A growing body of evidence suggests that brain insulin resistance promotes or possibly is the trigger of key pathologies in AD and is supported by observed changes in levels of insulin signaling molecules in AD forebrains and associated changes in memory. Pre-clinical studies in animals have demonstrated the insulin sensitizing activity of T3D-959 and ability to improve multiple pathologies of AD in a rat model of disease. 