Life-long rapamycin administration reduces Aβ levels and deposition.

<p>(<b>A–I</b>) Representative sections from brains of 3xTg-AD^CTL, 3xTg-AD^15–18 and 3xTg-AD^2–18 mice (n = 8/group) immunostained with an Aβ-specific antibody (A–B, D–E, G–H) and stained with thioflavin S (C, F, I), clearly show that the 3xTg-AD^2–18 mice have less diffuse and fibrillar Aβ deposits compared to 3xTg-AD^CTL and 3xTg-AD^15–18 mice. (<b>J</b>) Semi-quantitative assessment of the number of thioflavin-positive plaques shows no significant change between 3xTg-AD^CTL and 3xTg-AD^15–18 mice. In contrast, the 3xTg-AD^2–18 mice have significantly less plaques compared to the other two groups. One-way ANOVA across the three different groups shows that the changes were highly significant (F = 69.65; p<0.0001). Panels B, E and H represent high magnification views of panels A, D and G. (<b>K–L</b>) Soluble (K) and insoluble (L) Aβ40 and Aβ42 levels were measured by sandwich ELISA. Consistent with the histological results, compared to 3xTg-AD^CTL mice, soluble and insoluble Aβ40 and Aβ42 levels were significantly reduced only in the 3xTg-AD^2–18 mice (F = 40.50; p<0.0001 for the soluble Aβ levels; F = 22.51 and p<0.0001 for the insoluble Aβ levels). Data are presented as means ± SEM.