Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s disease

• DOI: 10.1186/s40478-020-01099-x
• Publication Date: 2021-01-05T14:03:48Z
• Authors: Akira Sobue; Okiru Komine; Yuichiro Hara; Fumito Endo; Hiroyuki Mizoguchi; Seiji Watanabe; Shigeo Murayama; Takashi Saito; Takaomi C. Saido; Naruhiko Sahara; Makoto Higuchi; Tomoo Ogi; Koji Yamanaka
• Keywords: Mice, Transgenic; Amyloid beta-Protein Precursor; Mice; 03 medical and health sciences; Neuroinflammation; Alzheimer Disease; Parietal Lobe; Animals; Homeostasis; Humans; Animal model; Next generation sequence; RNA-Seq; RC346-429; 0303 health sciences; Precuneus; Superoxide Dismutase; Research; Amyotrophic Lateral Sclerosis; Tauopathies; Case-Control Studies; Neurology. Diseases of the nervous system; Microglia; Transcriptome; Alzheimer’s disease

Abstract Microglia-mediated neuroinflammation has been implicated in the pathogenesis of Alzheimer’s disease (AD). Although microglia aging and neurodegenerative model mice show a loss homeostatic phenotype activation disease-associated (DAM), correlation between those phenotypes degree neuronal cell not clarified. In this study, we performed RNA sequencing isolated from three representative mouse models, App NL - G F/NL F with amyloid pathology, rTg4510 tauopathy, SOD1 G93A motor neuron by magnetic activated sorting. parallel, gene expression patterns human precuneus early change (n = 11) control brain 14) were also analyzed sequencing. We found that substantial reduction microglial genes microglia, whereas DAM uniformly upregulated all models. The was correlated loss. AD reduced related to microglia- oligodendrocyte-specific markers observed, although upregulated. Our results implicate function progression other diseases. Moreover, analyses suggest oligodendrocyte functions induced pathology human.