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Although microglia in aging and neurodegenerative disease model mice show a loss of homeostatic phenotype and activation of disease-associated microglia (DAM), a correlation between those phenotypes and the degree of neuronal cell loss has not been clarified. In this study, we performed RNA sequencing of microglia isolated from three representative neurodegenerative mouse models, AppNL-G-F/NL-G-F with amyloid pathology, rTg4510 with tauopathy, and SOD1G93A with motor neuron disease by magnetic activated cell sorting. In parallel, gene expression patterns of the human precuneus with early Alzheimer's change (n=11) and control brain (n=14) were also analyzed by RNA sequencing. We found that a substantial reduction of homeostatic microglial genes in rTg4510 and SOD1G93A microglia, whereas DAM genes were uniformly upregulated in all mouse models. The reduction of homeostatic microglial genes was correlated with the degree of neuronal cell loss. In human precuneus with early AD pathology, reduced expression of genes related to microglia- and oligodendrocyte-specific markers was observed, although the expression of DAM genes was not upregulated. Our results implicate a loss of homeostatic microglial function in the progression of AD and other neurodegenerative diseases. Moreover, analyses of human precuneus also suggest loss of microglia and oligodendrocyte functions induced by early amyloid pathology in human. Overall design: We analyzed gene expression in microglia isolated by magnetic-activated cell sorting (MACS) from cerebral cortex of AppNL-G-F/NL-G-F and rTg4510 mice or lumbar spinal cord of SOD1G93A mice."],"tag":["xref:PubMed:33402227"],"repository":["ENA"],"description_synonyms":["Alzheimer Senile Dementia, Presenile Alzheimer Dementia, Senile, Disease, Alzheimer disease, ALZHEIMERS DIS, Materials, Alzheimers Diseases, Alzheimer Syndrome, Acute Confusional Senile Dementia, Early Onset, Sclerosis, brain-resident macrophage, familial, Gene, Early Onset Alzheimer Disease, Focal Onset, Dementia of the Alzheimer's type., Cistrons, Cell, Alzheimer's Dementia, Alzheimer's disease, unspecified (disorder), Primary Senile Degenerative Dementia, Microglial, [X]Dementia in Alzheimer's disease (disorder), Alzheimer Type, Alzheimer Dementias, ALZHEIMER DIS, Primary Senile Degenerative, AD, unspecified, [X]Dementia in Alzheimer's disease, Alzheimer's Diseases, Genetic Materials, Progressive neurodegenerative disorder, NOS, Microglias, Genetic Material, Dementia, MF.microglia.CNS, microglial cell, LATE ONSET ALZHEIMER DIS, Alzheimers, Familial Alzheimer Disease (FAD), Genetic, Alzheimer Diseases, Hortega cell, DAT - Dementia Alzheimer's type, Dementia in Alzheimer's disease, Alzheimer, Microglial Cell, Alzheimer's Disease Pathway, Dementias, Alzheimer Type Senile Dementia, INSDC_feature:gene, Neurodegenerative disease, Alzheimer-Type (ATD), Focal Onset Alzheimer's Disease, Late Onset Alzheimer Disease, Alzheimer Dementia, microgliocyte, microglia, Alzheimer Sclerosis, FOCAL ONSET ALZHEIMERS DIS, Presenile Dementia, Senile Dementia, Late Onset, Material, AD - Alzheimer's disease, Alzheimer Disease, Familial (FAD), Alzheimer Type Dementia, Acute Confusional, Dementia in Alzheimer's disease (disorder), Alzheimer-Type Dementia (ATD), Cistron, brain macrophage, hortega cells, ALZHEIMER DIS EARLY ONSET, Alzheimer's Disease, Alzheimer's disease (disorder), Presenile, Alzheimers Dementia, Familial Alzheimer Diseases (FAD), Neuro-degenerative disease, Alzheimers disease, Microglial Cells, Alzheimer Type Dementia (ATD)"],"name_synonyms":["Alzheimer Senile Dementia, Presenile Alzheimer Dementia, Senile, Disease, Alzheimer disease, ALZHEIMERS DIS, Materials, Alzheimers Diseases, Alzheimer Syndrome, Acute Confusional Senile Dementia, Early Onset, Sclerosis, brain-resident macrophage, familial, Gene, Early Onset Alzheimer Disease, Focal Onset, Dementia of the Alzheimer's type., Cistrons, Cell, Alzheimer's Dementia, Alzheimer's disease, unspecified (disorder), Primary Senile Degenerative Dementia, Microglial, [X]Dementia in Alzheimer's disease (disorder), Alzheimer Type, Alzheimer Dementias, ALZHEIMER DIS, Primary Senile Degenerative, AD, unspecified, [X]Dementia in Alzheimer's disease, Alzheimer's Diseases, Genetic Materials, Progressive neurodegenerative disorder, NOS, Microglias, Genetic Material, Dementia, MF.microglia.CNS, microglial cell, LATE ONSET ALZHEIMER DIS, Alzheimers, Familial Alzheimer Disease (FAD), Genetic, Alzheimer Diseases, Hortega cell, DAT - Dementia Alzheimer's type, Dementia in Alzheimer's disease, Alzheimer, Microglial Cell, Alzheimer's Disease Pathway, Dementias, Alzheimer Type Senile Dementia, INSDC_feature:gene, Neurodegenerative disease, Alzheimer-Type (ATD), Focal Onset Alzheimer's Disease, Late Onset Alzheimer Disease, Alzheimer Dementia, microgliocyte, microglia, Alzheimer Sclerosis, FOCAL ONSET ALZHEIMERS DIS, Presenile Dementia, Senile Dementia, Late Onset, Material, AD - Alzheimer's disease, Alzheimer Disease, Familial (FAD), Alzheimer Type Dementia, Acute Confusional, Dementia in Alzheimer's disease (disorder), Alzheimer-Type Dementia (ATD), Cistron, brain macrophage, hortega cells, ALZHEIMER DIS EARLY ONSET, Alzheimer's Disease, Alzheimer's disease (disorder), Presenile, Alzheimers Dementia, Familial Alzheimer Diseases (FAD), Neuro-degenerative disease, Alzheimers disease, Microglial Cells, Alzheimer Type Dementia (ATD)"],"additional_accession":[]},"is_claimable":false,"name":"Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer's disease","description":"Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer's disease","dates":{"last_updated":"2025-09-24","first_public":"2023-07-11"},"accession":"PRJNA989600","cross_references":{"GEO":["GSE236268"],"taxon":["10090"],"PubMed":["33402227"]}}