Fig. 3.

Initial sex-dependent amyloid plaque development in 5xFAD/Trem2^R47H mice. a Schematic showing mouse groups and study design. b, j Representative hemispheric coronal brain images of (b) 4-month-old and (j) 12-month-old 5xFAD and 5xFAD/Trem2^R47H stained for dense-core plaques using Thioflavin-S (green) with insets of higher magnification images of the (c, k) visual cortex and (e, m) subiculum. Scale bar = 500 µm. c, d In 4-month-old mice, there is a sex-dependent difference in density of Thio-S⁺ dense-core plaque burden within 5xFAD/Trem2^R47H in the visual cortex (c, plaque density; d, plaque volume; vertical significance bars). d, f Average plaque volumes showed no difference in (d) the visual cortex but decreased in (f) the subiculum of 5xFAD/Trem2^R47H compared to 5xFAD. g Reduced mean plaque intensity in 5xFAD/Trem2^R47H compared to 5xFAD at 4-months of age. h Quantification of total volume of OC⁺ diffused plaques in the subiculum shows less diffused plaques in 5xFAD/Trem2^R47H compared to 5xFAD at 4 months. i, q Representative confocal images of immunostained subiculum for OC (red) and Thio-S (green) at (i) 4-months and (q)12-months. k, m In 12-month old mice, there was no difference in density of dense-core plaques in the visual cortex of 5xFAD and 5xFAD/Trem2^R47H mice (k) but an increase in the subiculum (m). l, n No difference was observed in average plaque volume in (l) the cortex and (n) subiculum although there was a trend towards male 5xFAD/Trem2^R47H mice having larger plaques than females in (l) the cortex. o At 12 months, total mean plaque intensity is greater in 5xFAD/Trem2^R47H compared to 5xFAD. p Total volume of OC⁺ diffused plaques in the subiculum show lesson difference in diffuse plaques in 5xFAD/Trem2^R47H. n = 10–12. Data are represented as mean ± SEM. Student’s t-test. Statistical significance is denoted by *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Statistical trends are given by # 0.05 < p < 0.1