Review Article Reevaluating Metabolism in Alzheimer’s Disease from the Perspective of the Astrocyte-Neuron Lactate Shuttle Model

Copyright © 2013 Jordan T. Newington et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The conventional view of central nervous system (CNS)metabolism is based on the assumption that glucose is the main fuel source for active neurons and is processed in an oxidative manner. However, since the early 1990s research has challenged the idea that the energy needs of nerve cells are met exclusively by glucose and oxidative metabolism.This alternative view of glucose utilization contends that astrocytes metabolize glucose to lactate, which is then released and taken up by nearby neurons and used as a fuel source, commonly known as the astrocyte-neuron lactate shuttle (ANLS) model. Once thought of as a waste metabolite, lactate has emerged as a central player in the maintenance of neuronal function and long-term memory. Decreased neuronal metabolism has traditionally been viewed as a hallmark feature of Alzheimer’s disease (AD).However, amore complex picture of CNSmetabolism is emerging thatmay provide valuable insight into the pathophysiological changes that occur during AD and other neurodegenerative diseases. This review will examine the ANLS model and present recent evidence highlighting the critical role that lactate plays in neuronal survival andmemory.Moreover, the role of glucose and lactatemetabolism inADwill be re-evaluated from the perspective of the ANLS. 1