[Research advances on the triad of glucose metabolism, neuroinflammation and oxidative stress in driving Alzheimer's disease].

Research on the pathomechanism of Alzheimer's disease (AD) has long focused on β-amyloid (Aβ) deposition and Tau protein hyperphosphorylation. However, recent metabolomics studies have revealed that brain energy metabolism disorders occur in the early stages of AD. This paper systematically integrates the latest evidence and proposes the "metabolism-inflammation-oxidative stress triangle" hypothesis to elucidate the pivotal role of glucose metabolism network dysregulation in AD pathology. The results demonstrate that AD patients exhibit abnormal activity of key glycolysis enzymes, impaired insulin signaling pathways and mitochondrial oxidative phosphorylation dysfunction. These metabolic disturbances form a bidirectional positive feedback loop with neuroinflammation and oxidative stress through mechanisms including the metabolic reprogramming of microglial cells, the release of damage-associated molecular patterns (DAMPs), and activation of nuclear factor κB/mitogen-activated protein kinase (NF-κB/MAPK) pathway. This interplay drives Aβ and Tau deposition, as well as the oxidative stress, creating a vicious cycle of Aβ deposition and Tau phosphorylation. This paper reveals the central role of brain metabolic disorders as an early driver of AD, and emphasizes the therapeutic potential of multi-target strategies targeting key interaction nodes within the metabolism-inflammation-oxidative stress, which provides a novel theoretical framework for early AD intervention.