Extended Data Fig. 7: Target specificity and glial responses in LV- αAβ-Gas6 injected mice.

a, b, d, Representative confocal z-stack images of astrocytes (S100β, magenta), microglia (IBA1, red), ZsGreen (green), and DAPI (blue) in the CA1 of LV-Control-injected mouse (a). Orange and cyan arrows indicate ZsGreen⁺ astrocytes and microglia, respectively. Scale bar = 100 μm. Enlarged images of ZsGreen⁺ astrocyte (top) and microglia (bottom) are shown in b. Scale bar = 10 μm. Quantification bar graph of ZsGreen⁺ cell ratio (Microglia / Astrocyte) (d). n = 17, 15, 18. c, e, Representative confocal z-stack images of Aβ plaques (Congo Red, magenta) and ZsGreen (green) in the CA1 of LV-Control (left) and LV-αFITC-Gas6-injected (right) 5xFAD mouse brains. Scale bar = 100 μm (c). Quantification bar graphs of plaque number (left) and area (right) in the CA1 of LV-Control and LV-αFITC-Gas6-injected 5xFAD mouse brains (e). n = 11, 11. f, l, Representative confocal z-stack images of dystrophic neurites (LAMP1, green) and Aβ (6E10, red) in LVs-injected 5xFAD mouse brains. Right panels are enlarged images of orange dotted box in the left and middle panels. Scale bars = 100 μm (f). Quantification bar graph of LAMP1⁺ dystrophic neurites area (l). n = 40, 40, 32. g, h, m, Representative confocal z-stack images of TAM receptors (g, top: AXL; bottom: MERTK, red), glial cells (h, top: S100β; bottom: IBA1, red), αAβ-Gas6 (HA, green), and Aβ plaques (6E10, blue). Scale bars = 10 μm (g, h). Quantification bar graph of αAβ-Gas6 area associated with glial cells around Aβ plaques (m). n = 7, 7. i, n, o, Representative confocal z-stack images of GFAP (i) in the CA1 of LV-Control, LV-Aducanumab, and LV-αAβ-Gas6-injected mice. Scale bars = 40 μm (i). Quantification of the area (n) and intensity (o) of GFAP in the imaging fields. n = 6, 8, 6. j, k, p, q, Representative confocal z-stack images of plaque-associated microglia (PAM, j) and non-plaque-associated microglia (NPAM, k) in the CA1 of WT (k) and LV-injected 5xFAD mice (j, k) stained with microglia (IBA1, blue), CD68 (red) and Aβ plaques (no. 2454, green). Scale bars = 10 μm. Quantification of the areas of IBA1 and CD68 in PAM (normalized by plaque area) (p) and NPAM (q). n = 19, 21, 21 (p, left); n = 19, 21, 19 (p, right); n = 28, 25, 22, 24 (k, left); n = 19, 24, 22, 23 (k, right). One-way ANOVA followed by Tukey’s multiple comparison test. p, Two-sided unpaired Student’s t-test. Mean ± s.e.m.; n value represents independent experiments from 3 to 5 mice per group (d, e, k-p).

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