Perspectives of pharmacotherapy in Alzheimer's disease

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 neur onal loss. The senile plaques are composed of amyloid beta-peptides (A beta ), 40-42 amino acid peptide fragments of the beta-amyloid precursor protein . Genetic, molecular biological and neuropharmacological evidence support t he 'amyloid cascade hypothesis' for the pathogenesis of the disease. We rev iew the in vivo effects of various compounds on behavioral and neuropatholo gical changes in the non-transgenic animal models of AD produced by continu ous i.c.v. infusion of A beta. These results support therapeutic strategies such as cholinergic therapy, anti-inflammatory agents, antioxidants and es trogen replacement therapy, as well as other cognition enhancers for the tr eatment of AD. In addition, the amyloid cascade hypothesis offers a number of potential targets for novel therapeutic strategies in AD. We believe tha t our non-transgenic animal model, as well as transgenic animal models, are useful for developing novel pharmacotherapeutics in AD.