Altered Metabolism in Alzheimer Disease Brain: Role of Oxidative Stress.

Significance: Alzheimer disease (AD) is an all-too-common condition in the aging population. However, aging does not automatically equal neurodegeneration and memory decline. Recent Advances: This review article involves metabolic changes in the AD brain that are related to oxidative stress. Selected pathways are identified as potential targets for intervention in AD. Critical Issues: One of the main factors of AD is the oxidative imbalance within the central nervous system, causing a disruption in metabolic processes. Reactive oxygen species (ROS) are a natural consequence of many cellular processes, especially those associated with mitochondria, such as the electron transport chain. Some ROS, when kept under control and maintained at reasonable levels, often play roles in cell signaling. The cellular damage of ROS arises when oxidative imbalance occurs, in which case ROS are not controlled, leading to a myriad of alterations in cellular metabolic processes. These altered pathways include, among others, dysfunctional glycolysis, calcium regulation, lipid metabolism, mitochondrial processes, and mammalian target of rapamycin pathway dysregulation. Future Directions: Understanding how ROS can lead to these alterations can, ideally, elucidate therapeutic options for retarding AD progression in the aging population. Antioxid. Redox Signal. 36, 1289-1305.