Fig. 6: Chronic XBD173 treatment reduces the increase in astrocytic engulfment of C1q complement protein.

A Representative images for GFAP (red) and C1q (cyan) in the cortex in different experimental groups. The first panel shows the original image and the second panel shows the colocalization point (white) inside the rendered volume of the astrocyte from the respective groups. Scale bar: 5 µm. B Representative images for GFAP (red) and C1q (Cyan) in the hippocampus in different experimental groups. The first panel shows the original image and the second panel shows the colocalization point (white) inside the rendered volume of the astrocyte from the respective groups. Scale bar: 5 µm. C % of C1q engulfment by astrocyte quantified in different treatment groups in the cortex (Kruskal–Wallis test with a Dunn’s multiple comparisons post hoc test; WT: 0.7465 (0.0033–1.767) % vs Arc Aβ + vehicle: 3.448 (3.071–4.300) %, p < 0.0001; Arc Aβ + vehicle vs Arc Aβ + XBD: 0.6829 (0.1004–1.543) %, p < 0.0001; 15–23 astrocytes collected from 4–5 mice per group). D % of C1q engulfment by astrocyte quantified in different treatment groups in the hippocampus (Kruskal–Wallis test with a Dunn’s multiple comparisons post hoc test; WT: 0.8102 (0.1865–1.250) % vs Arc Aβ + vehicle: 5.056 (3.849–6.986) %, p < 0.0001; Arc Aβ + vehicle vs Arc Aβ + XBD: 0.4372 (0.1979–1.733) %, p < 0.0001; 26 astrocytes per collected from 5 mice per group). E Representative 63X images of C1q aggregate (magenta), methoxy-04 plaques (blue), merged, and colocalization (white) in transgenic AD mice. Scale bar: 20 um. F % plaque C1q interaction in different treatment groups. (Mann–Whitney U test: Arc Aβ + vehicle: 32.18 (25.07–54.76) % vs Arc Aβ + XBD: 37.99 (20.39–58.68) %, p = 0.9390; 13–16 astrocytes collected from 4 mice per group). G Orthogonal plane representation of GFAP (red) and Plaque (blue) interaction H. Representative image for GFAP (red) and Plaque (blue) interaction. The inset shows an enlarged section of the interaction with colocalization marked by white arrows. I Reconstructed astrocytes (red) after removal of background signal along with methoxy-04 (blue). J The colocalization of GFAP and methoxy-04 plaque is shown in white. Scale bar: 20 µm. K % plaque GFAP interaction in different treatment groups in the cortex and hippocampus. Arc Aβ + vehicle and Arc Aβ + XBD (Mann–Whitney U test: Arc Aβ + vehicle: 10.50 (5.305–17.99) % vs Arc Aβ + XBD: 14.15 (7.715–25.15) %, p = 0.3573; analysis from n = 21–24 plaques obtained from 4 mice per group) respective groups. H Orthogonal plane showing the GFAP (red) and synaptophysin (green). Scale bar: 5 µm. Data are represented as median with their respective interquartile range. *p < 0.05. ns: not significant.