The elevated H4K12la modification in amyloid-β (Aβ) plaque adjacent microglia activated the transcription of multiple genes encoding glycolytic enzymes, by which it ‘locked in’ the metabolic rewiring of microglia in AD and eventually drove the pro-inflammatory microglial activation by a positive feedback loop, termed as glycolysis/H4K12la/Pkm2 (Pan et al., 2022) (Figure 2). Here, PKM is linked to Alzheimer disease.