High Glucose Concentration on the Metabolic Activity of C6 Glia Cells: Implication in Alzheimer’s Disease

Background: Alzheimer’s disease (AD), the leading cause of dementia worldwide, poses an increasing global health burden, yet its pathogenesis remains poorly understood. Diabetes mellitus (DM), characterized by chronic hyperglycemia, has been identified as a significant risk factor for AD development, suggesting a potential metabolic and molecular link between these diseases. Methods: This study examines the impact of sustained high glucose levels on astrocyte-like C6 glial cells, focusing on key cellular processes associated with AD. We evaluated mitochondrial function, oxidative stress, glucose uptake, and the expression of hallmark AD proteins, including β-amyloid and hyperphosphorylated tau. Results: Our findings demonstrate that high glucose exposure triggers mitochondrial hyperactivity, oxidative stress, and increased Tau phosphorylation, though β-amyloid levels were unaffected within the experimental timeframe. Conclusions: These results shed light on the early cellular dysfunctions contributing to the DM-AD connection, providing valuable insights into the metabolic pathways involved and identifying potential therapeutic targets to mitigate AD progression in individuals with DM.