Creed Meaghan C, Milgram Norton W
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Age (Dordr). 2010 Sep;32(3):365-84. doi: 10.1007/s11357-010-9142-z. Epub 2010 Apr 20.
Alzheimer's disease (AD) is the most prevalent form of dementia, affecting an estimated 4.8 million people in North America. For the past decade, the amyloid cascade hypothesis has dominated the field of AD research. This theory posits that the deposition of amyloid-beta protein (Abeta) in the brain is the key pathologic event in AD, which induces a series of neuropathological changes that manifest as cognitive decline and eventual dementia. Based on this theory, interventions that reduce Abeta burden in the brain would be expected to alleviate both the neuropathological changes and dementia, which characterize AD. Several diverse pharmacological strategies have been developed to accomplish this. These include inhibiting the formation of Abeta, preventing the aggregation of Abeta into insoluble aggregates, preventing the entry of Abeta into the brain from the periphery and enhancing the clearance of Abeta from the central nervous system. To date, no amyloid-modifying therapy has yet been successful in phase 3 clinical trials; however, several trials are currently underway. This article provides a review of the status of amyloid-modifying therapies and the implications for the amyloid cascade hypothesis.
阿尔茨海默病（AD）是最常见的痴呆形式，在北美估计影响着480万人。在过去十年中，淀粉样蛋白级联假说主导了AD研究领域。该理论认为，大脑中β淀粉样蛋白（Aβ）的沉积是AD的关键病理事件，它会引发一系列神经病理变化，表现为认知能力下降并最终发展为痴呆。基于这一理论，减少大脑中Aβ负担的干预措施有望缓解AD所特有的神经病理变化和痴呆症状。为实现这一目标，已开发出多种不同的药理学策略。这些策略包括抑制Aβ的形成、防止Aβ聚集成不溶性聚集体、阻止Aβ从外周进入大脑以及增强中枢神经系统对Aβ的清除。迄今为止，尚无淀粉样蛋白修饰疗法在3期临床试验中取得成功；不过，目前有几项试验正在进行中。本文综述了淀粉样蛋白修饰疗法的现状及其对淀粉样蛋白级联假说的影响。
