Glucose Metabolism, Lactate, Lactylation and Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by cognitive decline; however, its pathogenesis remains incompletely understood. In recent years, the role of lactate metabolism and its derived lactylation modifications in AD has received increasing attention. As a product of glycolysis, lactate is not only a key molecule in energy metabolism but also regulates gene expression and protein function through lactylation modifications. Studies have shown that in the brains of AD patients, glucose metabolism is significantly reduced, while glycolysis is upregulated, and lactate levels are elevated. Nevertheless, the research regarding the relationship between lactylation and AD remains limited. Building on recent advances in understanding lactylation in neurodegenerative diseases and related conditions, we analyze and explore the potential relationships between lactylation and AD from the perspectives of β-amyloid (Aβ) deposition, tau protein pathology, and neuroinflammation. In summary, lactylation, as a novel post-translational modification holds significant promise in elucidating the pathological mechanisms and advancing the treatment of AD. A deeper investigation into its molecular mechanisms and regulatory networks may open new avenues for the diagnosis and treatment of AD.