Fig. 6From: Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s diseaseComparative 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)Back to article page