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Fig. 6 | Acta Neuropathologica Communications

Fig. 6

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

Fig. 6

Comparative gene expression analysis of human precuneus of Alzheimer’s disease (AD) brain with microglia isolated from the AD mouse models with amyloid and Tau pathology. a Schematic overview of the comparative expression analysis of the genes defined as risk factors for AD in human AD precuneus and microglia isolated from AppNL-G-F/NL-G-F and rTg4510 mice. b Venn diagram displaying the differentially expressed AD risk genes among each comparison (q < 0.05, |FC| > 1.5, cut-off TPM > 5). Upregulated and downregulated genes were shown in red and black, respectively. HBEGF/Hbegf was the only gene commonly deregulated (AD: log2FC = −0.843, q = 0.00861, AppNL-G-F/NL-G-F: log2FC = −1.710, q = 1.32E−23; rTg4510: log2FC = −0.738, q = 1.97E−05). Cd2ap, Mef2c, Plcg2, Sppl2a, Zcwpw1, Ptk2b and Clu were altered specifically in AppNL-G-F/NL-G-F microglia. Sorl1 and Il1rap were specifically deregulated in rTg4510 microglia. Apoe, Scimp, Pld3, Psen1, Psen2, Sqstm1, Trem2, Treml2, Ap2a2, Cass4, and Lmo4l were commonly altered in AppNL-G-F/NL-G-F and rTg4510 microglia. c, d Quantitative PCR analysis to determine expression level for HBEGF/Hbegf mRNA in human precuneus and isolated-microglia from each mouse model. c HBEGF expression level (FC = −1.83, p = 0.00560). d Hbegf expression level (AppNL-G-F/NL-G-F: FC = −1.98, p = 0.000272; rTg4510: FC = −2.19, p = 0.00277). Data are represented as the mean ± SEM. *p < 0.05, **p < 0.001. Bonferroni-corrected Student’s t test. c non-AD (n = 14) and AD (n = 11). d WT (n = 3) and AppNL-G-F/NL-G-F (n = 4); Ctrl and rTg4510 (n = 3 for each genotype). WT, wild-type; Ctrl, control. e Schematic overview of the comparative expression analysis of microglia isolated from mice with amyloid or Tau pathology and human precuneus with early AD. f, g Venn diagrams displaying the number of significantly upregulated (f) and downregulated (g) genes among each comparison between human AD precuneus and microglia isolated from AD mice and controls: 708 deregulated genes (149 upregulated and 559 downregulated) in AD precuneus (non-AD: n = 14 and AD: n = 11; q < 0.05, |FC| > 1.2); 2993 deregulated genes (1196 upregulated and 1797 downregulated) in AppNL-G-F/NL-G-F microglia (n = 4 for each genotype); and 2381 deregulated genes (951 upregulated and 1430 downregulated) in rTg4510 microglia (n = 3 for each genotype) (q < 0.05, |FC| > 1.5, TPM > 5)

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