Correlation between cognitive deficits and A beta deposits in transgenic APP+PS1 mice

Doubly transgenic mAPP+mPS1 mice (15-16 months) had impaired cognitive func tion in a spatial learning and memory task that combined features of a wate r maze and a radial arm maze. Nontransgenic mice learned a new platform loc ation each day during 4 consecutive acquisition trials, and exhibited memor y for this location in a retention trial administered 30 min later. In cont rast, transgenic mice were, on average, unable to improve their performance in finding the hidden platform over trials. The cognitive performance of i ndividual mice within the transgenic group were inversely related to the am ount of A beta deposited in the frontal cortex and hippocampus. These findi ngs imply that mAPP+mPS1 transgenic mice develop deficits in cognitive abil ity as A beta deposits increase. These data argue that radial arm water maz e testing of doubly transgenic mice may be a useful behavioral endpoint in evaluating the functional consequences of potential AD therapies, especiall y those designed to reduce A beta load. (C) 2001 Elsevier Science Inc. All rights reserved.