Understanding the Neuronal Requirement for Glycolysis

The brain has a high energy demand and consumes large amounts of glucose. In Alzheimer’s disease (AD), glucose uptake is reduced, but the significance of this change for neurodegeneration is unclear. Furthermore, whether or not neurons directly take up glucose has been debated in the field. Indeed, the lactate‐shuttle hypothesis predicts that glucose is primarily metabolized by glia or astrocytes into lactate, which is subsequently delivered to neurons and utilized continuously under aerobic conditions. However, studies utilizing glucose analogs challenge that model, and support direct glucose uptake by neurons. Here, we sought to understand the essential role of the neuronal glucose metabolism, to provide a starting point for new approaches to understand and target metabolic changes in AD.