Publication: Microglial metabolism is a pivotal factor in sexual dimorphism in Alzheimer's disease
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Identifiers
Date
2021-06-10
Authors
Guillot-Sestier, Marie-Victoire
Araiz, Ana Rubio
Mela, Virginia
Gaban, Aline Sayd
O'Neill, Eoin
Joshi, Lisha
Chouchani, Edward T.
Mills, Evanna L.
Lynch, Marina A.
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Nature
Abstract
Age 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.
Description
MeSH Terms
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over
Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Metabolic Networks and Pathways::Glycolysis
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Transgenic
Medical Subject Headings::Anatomy::Nervous System::Neuroglia::Microglia
Medical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Sex Factors
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over
Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Metabolic Networks and Pathways::Glycolysis
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Transgenic
Medical Subject Headings::Anatomy::Nervous System::Neuroglia::Microglia
Medical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Sex Factors
DeCS Terms
CIE Terms
Keywords
Microglial metabolism, Sexual dimorphism, Alzheimer’s disease, Risk factors, Amyloidosis, Genes, Microglía, Metabolismo, Características sexuales, Enfermedad de Alzheimer, Factores de riesgo, Amiloidosis
Citation
Guillot-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):711