Figure 1.

Selective reduction of Aβ₄₂ levels in the APP/tau mice. A–C, To define the impact of replacing the mutant PS1 with the wild-type allele on the APP levels, we measured the steady-state levels of APP by semiquantitative Western blot in the brains of 3xTg-AD and APP/tau mice (n = 10 mice/group/time point). Panels A–C show representative Western blots for APP. β-Actin was used as a loading control. Quantification analysis shows that the steady-state levels of APP were similar between 3xTg-AD and APP/tau mice at all ages analyzed (data not shown). D–F, We next used sandwich ELISA to measure the Aβ levels in the brains of the 3xTg-AD and the APP/tau mice. Aβ₄₀ levels were similar between the two groups at all ages analyzed. In contrast, we found that the levels of Aβ₄₂ were selectively decreased in the brains of the APP/tau mice compared with age- and gender-matched 3xTg-AD mice. Notably, this difference is accentuated as the mice age.