Guillot-Sestier, Marie-VictoireAraiz, Ana RubioMela, VirginiaGaban, Aline SaydO'Neill, EoinJoshi, LishaChouchani, Edward T.Mills, Evanna L.Lynch, Marina A.2024-02-192024-02-192021-06-10http://hdl.handle.net/10668/4035http://hdl.handle.net/20.500.12105/18373Age and sex are major risk factors in Alzheimer's disease (AD) with a higher incidence of the disease in females. Neuroinflammation, which is a hallmark of AD, contributes to disease pathogenesis and is inexorably linked with inappropriate microglial activation and neurodegeneration. We investigated sex-related differences in microglia in APP/PS1 mice and in post-mortem tissue from AD patients. Changes in genes that are indicative of microglial activation were preferentially increased in cells from female APP/PS1 mice and cells from males and females were morphological, metabolically and functionally distinct. Microglia from female APP/PS1 mice were glycolytic and less phagocytic and associated with increased amyloidosis whereas microglia from males were amoeboid and this was also the case in post-mortem tissue from male AD patients, where plaque load was reduced. We propose that the sex-related differences in microglia are likely to explain, at least in part, the sexual dimorphism in AD.engVoRhttp://creativecommons.org/licenses/by/4.0/Microglial metabolismSexual dimorphismAlzheimer’s diseaseRisk factorsAmyloidosisGenesMicroglíaMetabolismoCaracterísticas sexualesEnfermedad de AlzheimerFactores de riesgoAmiloidosisAgedAttribution 4.0 International3411292910.1038/s42003-021-02259-y2399-3642Communications Biologyopen access