Impaired Pavlovian cued fear conditioning in Tg2576 mice expressing a human mutant amyloid precursor protein gene.

The processing of emotional and/or fear-related events is abnormal in patients with Alzheimer's disease. AD is accompanied by a number of neuropathological features, one of which is the deposition of amyloid plaques. The main aim of the present study was to examine the effects of a human amyloid precursor protein mutation on both the acquisition and expression of fear conditioning in Tg2576 mice. Sixteen-month-old, but not 4-month-old, transgenic mice showed aberrations in post-shock freezing during training. In a retention test carried out 24 h after training, Tg2576 mice showed comparable levels of conditioned fear elicited by contextual cues. However, freezing elicited by a tone conditioned stimulus was impaired in 16-month-old but not 4-month-old Tg2576 mice. The results are discussed with reference to the role of cue competition (overshadowing) in revealing fear conditioning deficits in Tg2576 mice.