Reduction in Aβ deposition in the APP/tau mice. To determine whether the onset and progression of Aβ deposition were altered by the selective reduction in Aβ42 levels, brain sections from 6-, 12-, and 18-month-old APP/tau and 3xTg-AD mice (n = 10 mice/group/time point) were stained using different anti-Aβ antibodies. A–D, As expected, robust intraneuronal immunoreactivity was detected in the brains of 6-month-old 3xTg-AD mice, whereas we found that the selective reduction of Aβ42 levels led to a significant reduction of the intraneuronal Aβ staining. E–H, Immunohistochemical analysis of sections from 12-month-old mice revealed several extracellular Aβ plaques in the CA1/subiculum region. In contrast, no plaques were detected in the brains of age- and gender-matched APP/tau mice. I–L, We next evaluated the brains of 18-month-old mice. In the 3xTg-AD mice, Aβ plaques were evident throughout the brain, whereas no plaques were detected in the APP/tau mice, and only a weak intraneuronal immunoreactivity was apparent.