Soluble Aβ40‐42 levels are elevated in all brain regions of 3N mice compared to the 2N counterparts by 7–8 months of age, with observed sex‐specific differences. At 7–8 months of age, soluble Aβ40‐42 is elevated in 3N mice in all four brain regions. (a) In the BF, soluble Aβ40 is significantly elevated in 3N vs. 2N mice and in females vs. males; a significant interaction was also shown, with 3N females showing the highest levels. (b) Aβ42 is significantly elevated in 3N vs. 2N mice and in females vs. males. (c–h) 3N mice showed elevated Aβ40‐42 levels in the FCtx, the Hp, and the Cere compared to 2N mice. Data are presented as means ± SEM. 2N vs 3N bars to the right illustrate the observed main effects of genotype. **p < 0.01, ***p < 0.001, ****p < 0.0001