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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

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

Fig. 3

Elevated gene expression of disease-associated microglia (DAM) in mouse models of neurodegenerative diseases. DAM gene expression analyzed by RNA sequencing (RNA-Seq) and quantitative PCR (WT: n = 4 and AppNL-G-F/NL-G-F: n = 4; Ctrl: n = 3 and rTg4510: n = 3; WT: n = 4 and SOD1G93A: n = 4). WT, wild-type; Ctrl, control. a A heat map of DAM genes in isolated-microglia. Colors indicate upregulated (blue) and downregulated genes (red) relative to each control. +: q < 0.05, ++: q < 0.001. b, c Quantitative PCR analysis to determine expression levels of Apoe and Itgax mRNA in isolated-microglia of each mouse model. b Apoe expression level (AppNL-G-F/NL-G-F: FC = 1.91, p = 0.0126; rTg4510: FC = 5.51, p = 0.0251; SOD1G93A: FC= 30.1, p = 0.000177). c Itgax expression level (AppNL-G-F/NL-G-F: FC = 15.3, p = 0.00638; rTg4510: FC = 12.4, p = 0.0129; SOD1G93A: FC = 16.1, p = 0.00138). Data are represented as the mean ± SEM. *p < 0.05, **p < 0.001. Bonferroni-corrected Student’s t test. d Log2FC values against WT/Ctrl for 162 DAM genes in the isolated microglia from the cortex of APPNL-G-F/NL-G-F and rTg4510 mice, and spinal cord of SOD1G93A mice. AppNL-G-F/NL-G-F (median log2FC = 1.466), rTg4510 (median log2FC = 1.275, adj. p = 2.12E−03), and SOD1G93A (median log2FC = 1.484, adj. p = 1.14E−01) mice. Data are represented as the median with 5th and 95th percentile. *p < 0.05, **p < 0.001. Wilcoxon’s signed rank test, followed by a multiple testing correction using the Bonferroni–Holm method. eg Representative immunofluorescent images demonstrating expression of Aβ, Tau, or SOD1 (thioflavin, white), Iba1 (green), and ApoE (red) in the cortex of e WT and AppNL-G-F/NL-G-F mouse, f Ctrl and rTg4510 mouse, and g the spinal cord of WT and SOD1G93A mouse. Arrowheads indicate Aβ and Aβ-associated microglia. Scale bars: 20 µm (e, f) and 50 µm (g)

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