Figure 4.

Amyloid plaque deposition and tau phosphorylation in TgF344-AD rats are unaffected by treatment with (−)-P7C3-S243. (A-E) Amyloid plaque deposition is significantly increased in TgF344-AD rats in the hippocampus, cerebral cortex, frontal cortex, and cerebellum, but is not affected by (−)-P7C3-S243 administration. (A) Representative images of Congo Red staining in the hippocampus are depicted and (B-E) quantified in the hippocampus, cerebral cortex, prefrontal cortex, and cerebellum using Cy5 intensity quantification. Hippocampus plaque treatment effect was F(1,21 )=0.8611, p=0.3640 and genotype effect was F(1,21 )=135.2, p<0.0001. Cerebral cortex plaque treatment effect was F(1,21 )=0.3161, p=0.5799 and genotype effect was F(1,21 )=115.3, p<0.0001. Prefrontal cortex plaque treatment effect was F(1,21 )=0.0571, p=0.8135 and genotype effect was F(1,21 )=104.3, p<0.0001. Cerebellum plaque treatment effect was F(1,21)=0.0203, p=0.8881 and genotype effect was F(1,21)=30.63, p<0.0001. The white bar represents 100 μm. (F, G) Soluble (triton) and insoluble (5 M guanidine HCl) Aβ 1-40 and Aβ 1- 42 peptides are elevated in TgF344-AD rats relative to WT animals at 15 months, regardless of sex or treatment. (H) Pathological tau in the form of insoluble (sarkosyl insoluble) hyperphosphorylated tau is elevated in all groups. (I) Flyperphosphorylated tau (anti-Tau PS199/202) immunostaining in the hippocampus is also similar between all experimental groups. Hippocampal tau ps^199/202 treatment effect was F(1,21)=0.0005, p=0.9832 and genotype effect was F(1,21)=0.0324, p=0.8589. Whole brain tau ps^199/202 treatment effect was F(1,20)<0.0001, p=0.9973 and genotype effect was F(1,20)=1.126, p=0.3012. For each measurement, n=6-7/group. Data are represented as mean ± SEM. Significance was determined using two-way ANOVA with Tukey’s post-hoc multiple comparison analysis. *p < 0.05; **p < 0.01; ***p<0.001; ****p<0.0001.