Pii: S0197-4580(00)00249-9

Doubly transgenic mAPP1mPS1 mice (15–16 months) had impaired cognitive function in a spatial learning and memory task that combined features of a water maze and a radial arm maze. Nontransgenic mice learned a new platform location each day during 4 consecutive acquisition trials, and exhibited memory for this location in a retention trial administered 30 min later. In contrast, transgenic mice were, on average, unable to improve their performance in finding the hidden platform over trials. The cognitive performance of individual mice within the transgenic group were inversely related to the amount of Ab deposited in the frontal cortex and hippocampus. These findings imply that mAPP1mPS1 transgenic mice develop deficits in cognitive ability as Ab deposits increase. These data argue that radial arm water maze testing of doubly transgenic mice may be a useful behavioral endpoint in evaluating the functional consequences of potential AD therapies, especially those designed to reduce Ab load. © 2001 Elsevier Science Inc. All rights reserved.