Perspectives of pharmacotherapy in Alzheimer's disease

Kiyofumi Yamada, Xiuhai Ren, Toshitaka Nabeshima

Research output: Contribution to journalReview articlepeer-review

22 Citations (Scopus)


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 β-peptides (Aβ), 40-42 amino acid peptide fragments of the β-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 Aβ. 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.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalJapanese Journal of Pharmacology
Issue number1
Publication statusPublished - 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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