Transgenic mice carrying both the human amyloid precursor protein (APP) with the Swedish mutation and the presenilin-1 A246E mutation (APP/PS1 mice) develop Alzheimer's disease-like amyloidβ protein (Aβ) deposits around 9 months of age. These mice show an age-dependent increase in the level of Aβ40 and Aβ42 and in the number of amyloid plaques in the brain. Aβ40 and Aβ42 levels were measured, and amyloid burden and plaque number were quantified, in the hippocampus at the age of 4, 12, and 17 months in both male and female APP/PS1 mice. In all mice, amyloid burden and plaque number increased markedly with age, with female mice bearing a heavier amyloid burden and higher plaque number compared to male mice of the same age, both at 12 and at 17 months of age. The level of both Aβ40 and Aβ42 significantly increased in female mice with age and was always significantly higher in female than in male mice of the same age. Further, there were significant correlations between amyloid burden and Aβ42 level in female mice and between amyloid burden and plaques in both female and male mice. Together these data show that female APP/PS1 mice accumulate amyloid at an earlier age and that they build up more amyloid deposits in the hippocampus than age-matched male mice. Together, these results provide new insights in the potential mechanisms of the observed gender differences in the pathogenesis of AD. © 2003 Elsevier Inc. All rights reserved.