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. 2019 Feb 27;6(3):554–574. doi: 10.1002/acn3.730

Figure 7.

Figure 7

AZ59 reduces PrPC level and reverses aberrant eEF2 and JNK signaling in APP/PS1 mice. (A) Representative immunoblots of synaptosomal PrPC, PSD‐95 and β‐Actin from brains of 14‐16‐month APP/PS1 mice after 1 week of antibody treatment at 100 mg/kg. (B) Quantification of (A). One week (two doses) of treatment at 100 mg/kg significantly reduced levels of synaptic PrP relative to PSD‐95 (*,P < 0.05). Analysis by two‐tailed t‐test. n = 13 mice per group, data are mean ± SEM. (C) Representative western blots of TBS insoluble, Triton X‐100 soluble total, and phospho‐eEF2 (T56) from hippocampi of 14‐month wild type and APP/PS1 mice after 5 weeks of treatment. (D) Quantification of C. There was a significant increase in the level of Triton X‐100 soluble phospho‐eEF2 (T56) normalized to total eEF2 in hippocampi of 14‐month APP/PS1 mice treated with IgG control compared to wild type controls (*,P < 0.05). There was no significant difference in phospho‐eEF2 (T56) between 14‐month wild type controls and AZ59 treated APP/PS1 mice. Analysis by one‐way ANOVA with Dunnett's multiple comparisons test. n = 7–24 mice per group, data are mean ± SEM. (E) Representative western blots of TBS insoluble, Triton X‐100 soluble total, and phospho‐JNK (T183/Y185) from hippocampi of 14‐month wild type and APP/PS1 mice after 5 weeks of antibody treatment. (F) Quantification of (E). There was a significant increase in the level of Triton X‐100 soluble phospho‐JNK (T183/Y185) normalized to total JNK of the larger JNK isoform (upper band) in hippocampi of 14‐month APP/PS1 mice treated with IgG control compared to wild type controls (**,P < 0.01). There was no significant difference in phospho‐JNK (T183/Y185) of this isoform between wild type controls and APP/PS1 mice treated at 20 mg/kg. There was a significant increase in the level of phospho‐JNK (T183/Y185) normalized to total JNK of the smaller JNK isoform (lower band) in aged APP/PS1 mice treated with IgG control compared to wild type controls (***,P < 0.001). There was no significant difference in phospho‐JNK (T183/Y185) of this isoform between wild type controls and APP/PS1 animals treated with AZ59 at 20 mg/kg. Analysis by one‐way ANOVA with Dunnett's multiple comparisons test. n = 7–24 mice per group, data are mean ± SEM.