Fig 1: ApoE is a chemoattractant that directs VCAM1-dependent chemotaxis of microglia.a, STRINGdb protein–protein interaction between VCAM1 (green) and Aß plaque-associated proteins (orange). b, Schematic diagram showing the protocol for injecting protein-coated beads followed by IL-33 treatment in APP/PS1 mice. c–e, Representative images (c) and bar plots showing the numbers of microglia (d) and MHC-II+ microglia (e) within the area of BSA-, ApoE-, CD44-, and ITGB2-coated beads after IL-33 treatment (Con: BSA: n = 3, ApoE: n = 6, CD44: n = 6, ITGB2: n = 4; IL-33: BSA: n = 5, ApoE: n = 6, CD44: n = 6, ITGB2: n = 5; two-way ANOVA with Šidák’s multiple comparisons test). Dotted line indicates bead area. Scale bar = 20 µm. f, Representative images showing the Vcam1-expressing microglia surrounding ApoE-coated beads after IL-33 treatment. Arrowheads indicate Vcam1-expressing microglia. Scale bars = 50 µm (left) and 20 µm (right). Experiment was repeated for three batches with similar results. g–i, Representative images (g) and bar plots showing the numbers of microglia (h) and MHC-II+ microglia (i) within the areas of beads coated with nonlipidated or lipidated ApoE in IL-33-treated APP/PS1 mice (nonlipidated: n = 7; lipidated: n = 7; two-tailed paired t-test). Dotted line indicates bead area. Scale bar = 20 µm. j–o, VCAM1 is essential for the ApoE chemotaxis of microglia after IL-33 treatment. j–l, Representative images (j) and bar plots showing the numbers of microglia (k) and MHC-II+ microglia (l) within the ApoE-coated bead areas after co-injection of rVCAM1 in IL-33-treated APP/PS1 mice (Fc: n = 6; rVCAM1: n = 6; two-tailed paired t-test). Dotted line indicates bead area. Scale bar = 20 µm. m–o, Representative images (m) and bar plots showing the numbers of microglia (n) and MHC-II+ microglia (o) within the ApoE-coated bead areas in IL-33-treated APP/PS1;VCAM1-icKO mice (wild-type [WT]: n = 6; icKO: n = 6; two-tailed unpaired t-test). Dotted line indicates bead area. Scale bar = 20 µm. All data are mean ± s.e.m.Source data