Trial to produce animal model of Alzheimer's disease by continuous infusion of β-amyloid protein into the rat cerebral ventricle

To develop an animal model of Alzheimer's disease, we investigated the toxicity of β-amyloid protein which is a component of senile plaques in Alzheimer's disease. β-Amyloid was infused into the cerebral ventricle of rats for 14 days using a mini-osmotic pump. The performance of habituation, water maze and passive avoidance tasks in β-amyloid protein treated rats was impaired. Choline acetyltransferase activity significantly decreased in the hippocampus both immediately and 2 weeks after cessation of the infusion. However, the learning impairment is recoverable 2 weeks after cessation of the infusion. Both immediately and 2 weeks after cessation of the infusion, glial fibrillary acidic protein immunoreactivity increased. Further, β- amyloid protein altered the staining of nuclei of cells in the hippocampus only 2 weeks after cessation. These results suggest that β-amyloid protein damages the central nervous system in vivo, and that this animal could be used as a model of Alzheimer's disease.