Development of animal models for Alzheimer's disease

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We have investigated to develop animal models for Alzheimer's disease (AD) by continuous infusion of beta-amyloid protein (Abeta) into the cerebral ventricle of rats. The results obtained during the aid are as follows :In rats continuously infused Abeta,1 impairments of learning and memory were observed.2 deposition, of Abeta and decrease of choline acetyltransferase activity were observed in the cerebral cortex and hippocampus which play key roles in learning and memory.3 expression of glial fibrillary acidic protein, an index of gliosis, was increased in the hippocampus.4 ciliary neurotrophic factor content was increased in the cerebral cortex and hippocampus.5 nicotine- or high-K-evoked release of acetylcholine and dopamine in the cortex/hippocampus and striatum, respectively, was decreased.6 less electrophysiologicalresponse against nicotine in the hippocampal CAl pyramidal cells was observed.7 disability on induction of long-term potentiation in the hippocampal CAl pyramidal cells was observed.8 decrease of nicotine-induced enhancement of paired-pulse facilitation in the hippocampal CAl pyramidal cells was observed.9 administration of cognitive enhancers such as nefiracetam, propentofylline, arginine-vasopressin derivatives, idebenone and alpha-tocopherol, improves impairments of learning and memory induced by Abeta infusion.These results suggest that continuous infusion of Abeta is a good method to prepare the animal model of AD,which exhibits similar features observed in human AD patients. Moreover, this model is useful to evaluate the novel compounds for treatment of AD.