Fig. 5
ApoE isoforms and sex differentially influence Aβ plaque deposition in APP/PS1/EKI mice. a Brain sections from 4-month-old APP/PS1/EKI mice were immunostained with anti-Aβ antibody (HJ3.4-biotin) and the extent of Aβ deposition in the cortex quantified. There was a significant effect of sex (F1,57 = 5.792, p = 0.0194) and apoE isoform (F2,57 = 4.356, p = 0.0174) but no interaction (F2,57 = 0.3269, p = 0.7225). Post hoc analysis comparing apoE isoform within each sex found a statistically significant increase in Aβ deposition in female apoE4-expressing mice compared to apoE3 (p = 0.0466), APP/PS1/E2F = 8 males, 10 female; APP/PS1/E3F = 9 males, 10 females; APP/PS1/E4F = 13 males, 13 females. Scale bar = 1 mm. b Brain sections from 4-month-old APP/PS1/EKI mice were stained with X-34 dye that recognizes only fibrillar plaques and the cortical area stained by X-34 was quantified. There was a significant effect of sex (F1,59 = 9.008, p = 0.0039) and apoE isoform (F2,59 = 4.838, p = 0.0113) but no interaction (F2,59 = 0.1898, p = 0.8276). Post hoc analysis comparing apoE isoform within each sex did not find a statistically significant difference, although there was a trend towards elevated X-34 staining in apoE4-expressing female mice compared to apoE2 (p = 0.0602) and apoE3 (0.0830), APP/PS1/E2F = 8 males, 9 females; APP/PS1/E3F = 11 males, 10 females; APP/PS1/E4F = 12 males, 15 females. Scale bar = 1 mm. c The density of plaques from 4-month old APP/PS1/EKI mice was calculated. There was a significant effect of sex (F1,57 = 5.101, p = 0.0278) and apoE isoform (F2,57 = 8.8085, p = 0.0008) but no interaction (F2,57 = 0.7514, p = 0.4763). Post hoc analysis comparing apoE isoform within each sex found a statistically significant increase in Aβ plaque density in female apoE4-expressing mice compared to apoE3 (p = 0.0032) or apoE2 (p = 0.0484), APP/PS1/E2F = 8 males, 10 females; APP/PS1/E3F = 9 males, 10 females; APP/PS1/E4F = 13 males, 13 females. d The average plaque size was quantified. There was a significant effect of sex (F1,57 = 5.410, p = 0.0236), but not of apoE isoform (F2,57 = 2.202, p = 0.1420) with no interaction (F2,57 = 0.05053, p = 0.9508), APP/PS1/E2F = 8 males, 10 females; APP/PS1/E3F = 9 males, 10 females; APP/PS1/E4F = 13 males, 13 females. e The density of X-34+ plaques was quantified. There was a significant effect of sex (F1,61 = 9.527, p = 0.0030) and apoE isoform (F2,61 = 9.941, p = 0.0002) but no interaction (F2,61 = 0.8835, p = 0.4186). Post hoc analysis comparing apoE isoforms within each sex found a statistically significant increase in plaque density in female apoE4-expressing mice compared to apoE3 (p = 0.0053), or apoE2 (p = 0.0016), APP/PS1/E2F = 8 males, 9 females; APP/PS1/E3F = 11 males, 10 females; APP/PS1/E4F = 14 males, 15 females. f The average X-34+ plaque size was quantified. There was a significant effect of sex (F1,61 = 11.97, p = 0.0010), but not apoE isoform (F2,61 = 2.094, p = 0.1320) with no interaction (F2,61 = 0.9353, p = 0.3980). All statistics were performed using a 2-way ANOVA followed by Tukey post-hoc test. *p < 0.05, **p < 0.01. All values are reported as mean ± SEM