A large series of 3-, 6-, 9-, and 12-month-old bigenic mice (N=240) with Swedish APP and A246E PS1 mutations was investigated in nest-building, spontaneous alternation, and two learning tasks. Progressive cognitive impairment was observed in APPswe/PS1 mice relative to controls for nest-building, spontaneous alternation, the reversal phase of left-right discrimination learning in a water-filled T-maze, and in retention of passive avoidance learning. The behavioral deficits in transgenic mice start at 6 months, appearing to offer an opportunity for assessing potential therapeutic agents in attenuating or preventing Alzheimer's disease.