Figure 1.

1.5-month old 5XFAD mice treated with 51657 for 7 weeks have reduced SPs and axonal dystrophy. A. Male 5XFAD mice treated with 51657 show reduced cortical SPs compared to those treated with vehicle that is evident in sections from bregma −1.96. B. Representative image of a cortical section (bregma −1.96) stained for APP (22C11; green) and SPs (NAB228; cyan), with the adjacent image showing annotation of SP-associated APP-positive processes, with exclusion of confounding APP-positive neuronal soma. C. Quantification of cortical Aβ (NAB228) integrated signal normalized to total measured area for combined bregma −1.96 and 0.2 analyses. A single high outlier mouse (p<0.05 by Grubb’s test) from both the male vehicle and 51657 group was omitted. Data were normalized to the mean of the male vehicle group, with n=3 vehicle- and 51657-treated male 5XFAD mice, and n=4 vehicle- and 51657-treated female 5XFAD mice. Statistical comparison of the male 5XFAD mice was by unpaired 2-tailed t-test (t=3.60, df=4). Error bars represent SEM. D. Correlation plot of the relative Aβ and plaque-associated APP signals from combined bregma −1.96 and 0.2 data for each 5XFAD study mouse after normalization to the vehicle mean for each sex. Data underwent linear fit analysis, with r² and p-value shown in the graph and dashed lines representing the 95% confidence interval. Circles=Vehicle; Squares=51657-treated.