Contribution of hyperglycemia-induced changes in microglia to Alzheimer's disease pathology

Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive and functional impairments. The investigation of AD has focused on the formation of senile plaques, composed mainly by amyloid beta (A beta) peptide, and neurofibrillary tangles (NFTs) in the brain. Senile plaques and NFTs cause the excessive recruitment and activation of microglia, thus generating neuroinflammation and neuronal damage. Among the risk factors for the development of AD, diabetes has increasingly attracted attention. Hyperglycemia, the fundamental characteristic of diabetes, is involved in several mechanisms that give rise to microglial overactivation, resulting in neuronal damage and cognitive impairment. Indeed, various studies have identified the correlation between diabetes and AD. The aim of this review is to describe various mechanisms of the hyperglycemia-induced overactivation of microglia, which leads to neuroinflammation and neuronal damage and consequently contributes to the pathology of AD. The disruption of the regulation of microglial activity by hyperglycemia occurs through many mechanisms, including a greater production of reactive oxygen species (ROS) and glycation end products (AGEs), and a decrease in the elimination of A beta. The future direction of research on the relation between hyperglycemia and AD is addressed, such as the importance of determining whether the hyperglycemia-induced harmful effects on microglial activity can be reversed or attenuated if blood glucose returns to a normal level. [GRAPHICS] .