PKM and Alzheimer disease: Elevated H4 K12 la levels are observed in AD brains, particularly in microglia surrounding β-amyloid (Aβ) plaques, where this modification activates glycolysis-related genes (PKM and LDHA), forming a “glycolysis-histone lactylation-PKM2” positive feedback loop that exacerbates lactate accumulation, neuroinflammation, Aβ deposition, and cognitive decline [11].