Fig 2: Bexarotene treatment corrects short-term memory deficits, and cognitive improvements are maintained after removal in vivo. Novel object recognition behavioral assay is displayed as the relative discrimination index for wildtype (WT)-vehicle and APP/PS1 (Tg)-vehicle or bexarotene-treated mice for each treatment group. The relative discrimination index (see the “Methods” section) was determined as the ratio between the difference in time spent investigating novel and familiar objects to the total time investigating both objects. Relative discrimination indexes of 0 represent lack of discrimination between novel and familiar object while values greater than 0 represent recognition of the novel object. **p < 0.01 and ***p < 0.001 with respect to WT vehicle and #p < 0.05 and ##p < 0.01 with respect to Tg vehicle, one-way ANOVA with Tukey post hoc test for multiple corrections. Fourteen days on (n = 10, 4, 6) and 14 days on + 14 days off (n = 14, 9, 10) for WT vehicle, Tg vehicle, Tg bexarotene, respectively. The 14 days on group contains mice that were subsequently tested in the 14 days on + 14 days off group

Fig 3: Neuritic dystrophy is increased in APPPS1–21 mice expressing the Trem2 R47H variant. a Immunohistochemistry was used to quantify dystrophic neurites in APPPS1–21;Trem2+/+ (n = 16), APPPS1–21;Trem2+/- (n = 15), and APPPS1–21;Trem2+/R47H (n = 10) mice by measuring (a) ubiquitin (magenta) and (b) N-terminal APP (n-APP, red) % area across the cortex and hippocampus. c Dystrophic neurite area (ubiquitin, magenta) normalized to plaque (6E10, blue) size was assessed in APPPS1–21;Trem2+/+ (n = 16), APPPS1–21;Trem2+/- (n = 15), and APPPS1–21;Trem2+/R47H (n = 10) mice. d The correlation between ubiquitin positive area and plaque size was plotted for one representative animal per Trem2 genotype and (e) r2 and (f) slope for the linear best fit lines were calculated. Data are presented as mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001