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