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Alzheimer’s disease

Lipid fuel for hungry-angry microglia

Microglia require a large amount of energy to clear plaques in the brains of people with Alzheimer’s disease. Leng et al. found that increased activity of the glycolytic enzyme hexokinase 2 (HK2) blocks microglial phagocytosis in Alzheimer’s disease. Inhibition of HK2 results in increased microglial energy production by a compensatory lipid metabolism response, restores phagocytosis and improves cognitive function.

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Fig. 1: Microglial ATP production by aerobic glycolysis dependent on an Aβ-induced increase in HK2 activity is insufficient to clear plaques, but inhibition of HK2 induces a switch to lipid metabolism.

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Correspondence to Inhee Mook-Jung.

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Choi, H., Mook-Jung, I. Lipid fuel for hungry-angry microglia. Nat Metab 4, 1223–1224 (2022). https://doi.org/10.1038/s42255-022-00647-0

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