Fig. 4

RVS paradigm: IAXO-101 treatment lowered Iba-1 coverage but had no effect on Aβ pathology and behavior in male E4FAD mice. Male 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). Treatment did not impact the percentage of area covered by GFAP in the B cortex (CX) [t(11.16) = 0.6788, p > 0.5] or the C hippocampus (HP) [t(13.87) = 0.1201, p > 0.5]. D Microglia Iba-1 coverage (green, scale bars: 1000 μm). IAXO-101 treatment lowered percentage area covered by Iba-1 in the E CX [t(8.742) = 4.186, p < 0.05] and the F HP [t(9.993) = 2.253, p < 0.5]. G Higher power magnification images of Iba-1 in the CX (green, scale bars: 50 μm). IAXO-101 treatment H lowered number of total microglia I but did not affect type 1 microglia [total: t(9.035) = 2.497, p < 0.05; type 1: t(10.00) = 0.3145, p > 0.5]. However, IAXO-101 treatment lowered J type 2/3 microglia [type 2/3: t(8.845) = 4.032, p > 0.1] and modified the K distribution of microglial subtypes. Surprisingly, there was no effect of IAXO-101 on the levels of IL-1β in the L CX [t(9.835) = 0.177, p > 0.5] and M the HP [t(5.356) = 1.348 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(7.636) = 0.8443, p > 0.1] and the P HP [t(12.63) = 1.643, p > 0.1] or in fibrillar amyloid (Q green, scale bars: 1000 μm) in the R CX [t(9.761) = 10.558, p > 0.5] and the S HP [t(13.47) = 0.2563, p > 0.5]. In the Morris water maze test, IAXO-101 treatment T had no effect on the learning/acquisition [2-way ANOVA-days: F(2.774,38.84) = 6.170, p < 0.01; treatment: F(1,14) = 0.064, p > 0.5] and U in the memory/probe trials [target quadrant: t(8.075) = 0.035, p > 0.5; platform t(7.641) = 1.134, p > 0.1]. 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