| The familial early-onset form of Alzheimer's disease has been linked to mutations in genes encoding the amyloid precursor protein (APP), presenilin 1 (PS1) or presenilin 2. Transgenic mouse models expressing a single or a combination of these gene mutations develop Alzheimer-like amyloidogenic neuropathology. Here we investigate behavioral changes in the doubly transgenic mouse line carrying a c-DNA copy of the Swedish mutation of the human APP gene together with a mutation of the human PS1 gene (APP + PS1). The transgenic APP + PS1 mice show at about 12 months of age a peak level of compact plaques in cortical brain areas. To investigate changes in learning, 14 APP + PS1 and 17 wild-type mice were tested on eyeblink classical conditioning, a form of associative learning that has been shown to be impaired in patients with Alzheimer's disease. The mice were trained either on the 500 ms trace (for which the hippocampus and cerebellum are essential) or 500 ms delay (for which the cerebellum is essential) conditioning procedure. In addition, the startle response, prepulse inhibition and rotarod were assessed in the 12 month-old mice. Results showed that the APP + PS1 mice exhibited normal performance on delay and trace conditioning when compared to wild-type littermates across a training period of 15 daily sessions. Since both groups exhibited a training-dependent increase in short-latency/startle responses, we compared both groups on percentage of conditioned responses adjusted for short-latency responses. Consistent with findings on the unadjusted percentage of conditioned responses, no group differences were evident in the residualized percentage of conditioned responses. Both groups exhibited a comparable level of startle responses and prepulse inhibition across a range of stimulus intensities. However, the APP + PS1 mice showed an impaired performance on the rotarod, suggesting a deficit in motor coordination in the APP + PS1 mice. The normal performance of the APP + PSI mice on eyeblink conditioning suggests that no severe dysfunction of the medial temporal lobe and cerebellar structures are present in 12 month old APP + PS1 mice. |
