Fig. 3

PVT paradigm: IAXO-101 has no effect on specific neuroinflammatory and behavioral readouts in male E4FAD mice. Male E4FAD mice were treated with IAXO-101 or vehicle from 4 to 6 months of age; PVT paradigm. A Representative image of mouse brains immunostained for GFAP (green, scale bars: 1000 μm). Treatment did not impact the percentage of area covered by GFAP in the B cortex (CX) [t(10.68) = 0.1806, p > 0.5] or the C hippocampus (HP) [t(9.084) = 1.503, p > 0.1]. D Microglia Iba-1 coverage (green, scale bars: 1000 μm). IAXO-101 treatment had no effect on percentage area covered by Iba-1 in the E CX [t(9.765) = 0.9540, p > 0.1] and the F HP [t(9.829) = 0.3946, p > 0.5]. G Higher power magnification images of Iba-1 in the CX (green, scale bars: 50 μm). IAXO-101 treatment H had no effect on number of total microglia I type 1 microglia, J type 2/3 microglia, K distribution of microglial subtypes [total: t(11.98) = 1.226, p > 0.1], type 1: t(10.73) = 0.09, p > 0.5; type 2/3: t(10.86) = 1.567, p > 0.1] or levels of IL-1β in the L CX [t(11) = 0.6826, p < 0.5] and M the HP [t(12) = 1.095, p > 0.1]. N Representative images of Aβ immunostaining (red, scale bars: 1000 μm). There was no effect of IAXO-101 on Aβ levels in the O CX [t(11.38) = 1.171, p > 0.1] and the P HP [t(9.549) = 0.7235, p > 0.1] or in fibrillar amyloid (Q green, scale bars: 1000 μm) in the R CX [t(11.45) = 1.07, p > 0.1] and the S HP [t(11.69) = 1.543, p > 0.1]. In the Morris water maze test, IAXO-101 treatment T had no effect on the learning/acquisition [2-way ANOVA-days: F(3.266,45.72) = 4.532, p < 0.01; treatment: F(1,14) = 1.056, p = 0.322] and U in the memory/probe trials [target quadrant: t(10.74) = 0.9724, p > 0.1; platform: t(11.48) = 0.004, p > 0.5]. Data are expressed as mean ± S.E.M. All data analyzed by Student’s t-test, except in Morris water maze acquisition trials (two-way repeated measures ANOVA). * p < 0.05. See Additional file 3 for n sizes and statistical analysis