Histone lactylation, specifically H4K12 lactylation, is significantly elevated in microglia (the resident macrophages of the brain) from both Alzheimer’s disease (AD) patients and 5XFAD mice, promoting the transcription of glycolytic genes, the positive feedback loop involving glycolysis, H4K12la, and PKM2 intensifies the dysfunction of microglia, and disrupting this loop has been shown to improve both microglial dysfunction and amyloid-beta (Aβ) pathology. This evidence concerns the gene PKM and Alzheimer disease.