Guillot-Sestier, Marie-VictoireAraiz, Ana RubioMela, VirginiaGaban, Aline SaydO'Neill, EoinJoshi, LishaChouchani, Edward T.Mills, Evanna L.Lynch, Marina A.2022-09-122022-09-122021-06-10Guillot-Sestier MV, Araiz AR, Mela V, Gaban AS, O'Neill E, Joshi L, et al. Microglial metabolism is a pivotal factor in sexual dimorphism in Alzheimer's disease. Commun Biol. 2021 Jun 10;4(1):711http://hdl.handle.net/10668/4035Age 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Microglial metabolismSexual dimorphismAlzheimer’s diseaseRisk factorsAmyloidosisGenesMicroglíaMetabolismoCaracterísticas sexualesEnfermedad de AlzheimerFactores de riesgoAmiloidosisMedical Subject Headings::Persons::Persons::Age Groups::Adult::AgedMedical Subject Headings::Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and overMedical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer DiseaseMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression RegulationMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Metabolic Networks and Pathways::GlycolysisMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, TransgenicMedical Subject Headings::Anatomy::Nervous System::Neuroglia::MicrogliaMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Sex Factorsresearch article34112929open access10.1038/s42003-021-02259-y2399-3642PMC8192523