Fig. 2

RVS paradigm: IAXO-101 lowers neuroinflammation and Aβ pathology and improves memory in female E4FAD mice. Female E4FAD mice were treated with IAXO-101 or vehicle from 6 to 7 months of age; RVS paradigm. A Representative image of mouse brains immunostained for GFAP (green, scale bars: 1000 μm). IAXO-101 treatment did not affect the percentage of area covered by GFAP in the B cortex (CX) [t(13.71) = 0.9136, p > 0.5] or the C hippocampus (HP) [t(9.278) = 1.448, p > 0.5]. D Microglia Iba-1 coverage (green, scale bars: 1000 μm). IAXO-101 treatment lowered Iba-1 coverage in the E CX [t(7.345) = 4.671, p < 0.01] and the F HP [t(8.823) = 2.309, p < 0.05]. G Higher power magnification images of Iba-1 in the CX (green, scale bars: 50 μm). IAXO-101 treatment H resulted in a lower number of total microglia [t(9.995) = 3.870, p < 0.001], and I did not affect type 1 microglia; however, J resulted in a lower number of type 2/3 microglia. K Percentage of type 1 and 2/3 microglia [type 1: t(9.998) = 0.2848, p > 0.1; type 2/3: t(9.793) = 4.073, p < 0.001]. Levels of IL-1β did not change with IAXO-101 treatment in the L CX [t(12.18) = 1.039, p > 0.1] and M the HP [t(7.979) = 0.928, p > 0.1]. N Representative images of Aβ immunostaining (red, scale bars: 1000 μm). IAXO-101 treatment lowered Aβ levels in the O CX [t(13.53) = 2.040, p = 0.06] and the P HP [t(11.46) = 2.294, p < 0.05]. IAXO-101 treatment lowered fibrillar amyloid (Q green, scale bars: 1000 μm) in the R CX [t(10.13) = 2.056, p = 0.06] and in the S HP [t(8.520) = 3.725, p < 0.01]. In the Morris water maze test, IAXO-101 treatment T had no effect on the learning/acquisition [2-way ANOVA-days: F(2.907,34.89) = 3.204, p < 0.05; treatment: F(1,12) = 2.807, p = 0.1197]; however, U in the memory/probe trial resulted in lower latency to quadrant and platform [target quadrant: t(8.663) = 1.7, p = 0.1248; platform: t(8.991) = 2.462, p < 0.05]. Data are expressed as mean ± S.E.M. All data analyzed by Student’s t-test, except in Morris water maze acquisition trials T (two-way repeated measures ANOVA). * p < 0.05. See Additional file 3 for n sizes and statistical analysis