Fig. 1

Tamoxifen administration reduces ApoE levels in Aldh1l1-Cre + APPPS1;FE3Cre- and APPPS1;FE4Cre- mice. A Timeline of the experimental scheme. Mice were given once-daily IP injections of tamoxifen (TAM) (100 mg TAM/kg body weight) at 4 weeks of age for 6 consecutive days. Sample collection and analysis occurred at 18 weeks of age. B APOE mRNA expression levels in Cre- and Cre + FE3, FE4, APPPS1;FE3, and APPPS1;FE4 mice. Cortical tissue samples were analyzed by qPCR (n = 9). C Soluble apoE levels in the cortex of Cre- or Cre + mice. Cortical tissue samples were homogenized in PBS and PBS-soluble apoE protein levels were analyzed by ELISA (n = 9–19). D Insoluble apoE levels in the cortex of Cre- or Cre + mice. PBS-insoluble cortex tissue samples from (C) were further homogenized in 5 M guanidine HCl to determine the amount of PBS-insoluble apoE that was guanidine-soluble. Protein levels were analyzed by ELISA (n = 9–19). E ApoE immunostaining in the cortex and hippocampus of Cre-and Cre + mice. Representative images are of female brain sections stained with an anti-apoE antibody. Scale bars = 300 μm. F Intensity of fluorescent apoE staining in Cre- or Cre + mice. The average pixel intensity was analyzed from images of apoE immunostained brain sections (n = 10–19). G Brain sections from female APPPS1;FE4Cre- and APPPS1;FE4Cre + mice co-stained for X-34 (blue), apoE (green), GFAP (red), and Iba1 (magenta). White arrows indicate co-localization of apoE with GFAP and green arrows indicate co-localization of apoE with Iba1. Scale bars = 50 μm. A-G * p ≤ 0.05, ** p ≤ 0.01, and **** p ≤ 0.0001; two-way ANOVA and Sidak’s post hoc test in (B), three-way ANOVA and Sidak’s post hoc test in (D); three-way ANOVA and uncorrected Fisher’s LSD test in (C) and (F). Data are expressed as mean ± SEM. See Supplementary Table 1 for detailed statistics