Jpn. J. Pharmacol. 80 (1), 9-14 (1999)

-Current Perspective-
Perspectives of Pharmacotherapy in Alzheimer's Disease

Kiyofumi Yamada, Xiuhai Ren and Toshitaka Nabeshima (*)

Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan
(*) To whom correspondence should be addressed.

Abstract: Alzheimer's disease (AD) is the most common cause of progressive decline of cognitive function in aged humans, and it is characterized by the presence of numerous senile plaques and neurofibrillary tangles accompanied by neuronal loss. The senile plaques are composed of amyloid beta-peptides (Abeta), 40 - 42 amino acid peptide fragments of the beta-amyloid precursor protein. Genetic, molecular biological and neuropharmacological evidence support the 'amyloid cascade hypothesis' for the pathogenesis of the disease. We review the in vivo effects of various compounds on behavioral and neuropathological changes in the non-transgenic animal models of AD produced by continuous i.c.v. infusion of Abeta. These results support therapeutic strategies such as cholinergic therapy, anti-inflammatory agents, antioxidants and estrogen replacement therapy, as well as other cognition enhancers for the treatment of AD. In addition, the amyloid cascade hypothesis offers a number of potential targets for novel therapeutic strategies in AD. We believe that our non-transgenic animal model, as well as transgenic animal models, are useful for developing novel pharmacotherapeutics in AD.

Keywords: Alzheimer's disease, beta-Amyloid, Animal model, Learning and memory

Copyrightę The Japanese Pharmacological Society 1999

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