Fig. 5: VCAM1–ApoE interaction is critical for the Aβ chemotaxis of microglia and microglia-mediated Aβ clearance after IL-33 treatment.
From: The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology
a–c, ApoE-neutralizing antibody inhibits the Aβ chemotaxis of microglia upon IL-33 treatment. a, Schematic diagram showing the protocol for ApoE-neutralizing antibody administration before IL-33 treatment in APP/PS1 mice. b,c, Representative images (b) and violin plot (c) showing the distance between chemotactic microglia (that is, Vcam1+ Cx3cr1+ cells) and the nearest Aβ plaque 24 h after administration of ApoE-neutralizing antibody in IL-33-treated APP/PS1 mice (IgG Con: n = 107 microglia from 6 mice; IgG IL-33: n = 115 microglia from 5 mice; αApoE Con: n = 94 microglia from 6 mice; αApoE IL-33: n = 93 microglia from 6 mice; Kruskal–Wallis test with Dunn’s multiple comparisons test). Dotted circle indicates 10 μm from the perimeter of the Aβ plaque. Arrowheads indicate Vcam1-expressing microglia. Scale bar = 10 μm. d–i, VCAM1–ApoE interaction is required for inducing the phagocytic state transition of microglia after the induction of VCAM1 expression. d–f, Representative images (d) and bar plots showing the proportions of Aβ plaque-associated microglia (e) and phagocytic microglia (f) (that is, MHC-II+ Iba1+ cells) 24 h after administration of ApoE-neutralizing antibody in IL-33-treated APP/PS1 mice (IgG Con: n = 5; IgG IL-33: n = 5; αApoE Con: n = 5; αApoE IL-33: n = 5; two-way ANOVA with Šidák’s multiple comparisons test). Arrowheads indicate phagocytic microglia. Scale bar = 20 μm. g–i, Representative images (g) and bar plots showing the proportions of Aβ plaque-associated microglia (h) and phagocytic microglia (i) (that is, MHC-II+ Iba1+ cells) 24 h after IL-33 treatment in APP/PS1-ApoE–knockout mice (n = 6 per condition; two-way ANOVA with Šidák’s multiple comparisons test). Scale bar = 20 μm. j,k, Representative images (j) and bar plot (k) showing the Aβ plaque areas in the cortex 48 h after administration of ApoE-neutralizing antibody in IL-33-treated APP/PS1 mice (IgG Con: n = 5; IgG IL-33: n = 7; αApoE Con: n = 4; αApoE IL-33: n = 4; two-way ANOVA with Šidák’s multiple comparisons test). Scale bar = 200 μm. All data are mean ± s.e.m.
