GSK3B and Alzheimer disease: Evaluation of the mechanism by which insulin improves outcomes in AD has demonstrated a multifaceted therapy; insulin can directly affect neurons by increasing glucose uptake or improving viability via non-metabolic pathways, while also contributing to the direct degradation of beta amyloid via insulin-degrading enzyme activation, downregulation of GSK-3β, and reducing cortisol expression, which can inhibit hippocampal glucose uptake (for review, see Frey, 2013).