Fig. 1

PVT paradigm: IAXO-101 lowers neuroinflammation and improves memory in female E4FAD mice. Female 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(13.46) = 0.5080, p > 0.5] or the C hippocampus (HP) [t(13.79) = 0.1996, p > 0.5]. D Microglia Iba-1 coverage (green, scale bars: 1000 μm). IAXO-101 treatment appeared to lower the percentage area covered by Iba-1 in the E CX [t(7.998) = 1.909, p = 0.093] and the F HP [t(7.259) = 2.608, 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(9.809) = 0.5045, p = 0.05], 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(10.81) = 1.456, p > 0.1; type 2/3: t(10.03) = 0.5080, p < 0.05]. Levels of IL-1β were lower with IAXO-101 treatment in the L CX [t(9) = 2.297, p < 0.05] and M the HP [t(9) = 2.499, p < 0.05]. 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(8.644) = 1.680, p > 0.1] and the P HP [t(13.86) = 1.031, p > 0.1]. IAXO-101 treatment increased fibrillar amyloid (Q green, scale bars: 1000 μm) in the R CX [t(6.953) = 2.608, p < 0.05] with no effect in the S HP [t(11.47) = 1.317, 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(3.111,40.45) = 11.93, p < 0.0001; treatment: F(1,13) = 1.011, p = 0.333]; however, U in the memory/probe trial resulted in lower latency to quadrant and platform [target quadrant: t(7.513) = 2.528, p < 0.05; platform: t(6.604) = 2.388, 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 (two-way repeated measures ANOVA). * p < 0.05. See Additional file 3 for n sizes and statistical analysis