Extended Data Fig. 8: Blocking Itgb8 signaling enhances MGnD response and reduces AD pathology in APP/PS1 mice.

a–c, Confocal images of Tmem119, Apoe, and Clec7a staining (a); P2ry12, Apoe, and Clec7a staining (b); Lgals3, Iba1, and Clec7a staining (c) in the cortex of Itgb8-cKO mice and littermate controls. Arrows indicate microglia. Data are representative of 2 independent experiments. Scale bar: 50 μm. d, Gene ontology network of increased DEGs in microglia from Itgb8-cKO mice compared to WT littermates. DEGs were identified using DESeq2 analysis with an LRT and gene ontology pathways selected with P < 0.05. e, PCA of each genotype. f, Heat map of DEGs of phagocytic- and non-phagocytic microglia isolated from WT and Itgb8-cKO mice. DEGs were identified using DESeq2 analysis with an LRT (n = 5-6 mice/group, P < 0.05). g, Gene ontology network of top pathways in phagocytic- and non-phagocytic microglia from Itgb8-cKO mice compared with WT mice. DEGs were identified using DESeq2 analysis with an LRT and gene ontology pathways selected with P < 0.05. h, FACS plot of Aβ phagocytosis in WT and Itgb8-cKO mice. Percentage calculated as Aβ42-Alexa Fluor 555⁺ out of Fcrls⁺CD11b⁺Ly6C^– microglia. i, Quantification of percentage of Aβ-42 phagocytic microglia in WT and Itgb8-cKO mice (n = 5 WT mice, n = 10 Itgb8-cKO mice). j, Confocal images of MHC II, Iba1, and HJ3.4B in APP/PS1 mice injected with anti-ITGB8 neutralizing antibody and IgG isotype control. Scale bar: 100 μm. k, Quantification of MHC II⁺ immunoreactivity at the injection site (n = 4 mice/group). Two-tailed Student’s t-test. Data were presented as mean ± s.e.m.