Geriatric Research and Education Center, North Hills, CA 91343, USA.
CNS Neurol Disord Drug Targets. 2010 Apr;9(2):140-8. doi: 10.2174/187152710791011991.
Alzheimer's disease (AD) is accompanied by an activation of the innate immune system, and many epidemiological studies have shown reduced risk for dementia or AD associated with chronic consumption of non-steroidal anti-inflammatory drugs (NSAIDs). These observations led to animal model studies to test the hypothesis that NSAIDs can be disease-modifying for some aspects of AD pathogenesis. NSAIDs cannot only suppress inflammatory targets, which could contribute to neuroprotection, they also slow amyloid deposition by mechanisms that remain unclear. Several large clinical trials with NSAID therapies with AD subjects have failed, and cyclooxygenase-2 does not appear to be a useful target for disease modifying therapy. However, there may be apolipoprotein E E4 pharmacogenomic effects and a real but delayed positive signal in a large primary prevention trial with naproxen. This encourages researchers to re-address possible mechanisms for a stage-dependent NSAID efficacy, the subject of this review.
阿尔茨海默病（AD）伴随着先天免疫系统的激活，许多流行病学研究表明，慢性使用非甾体抗炎药（NSAIDs）可降低痴呆或 AD 的风险。这些观察结果促使动物模型研究检验了 NSAIDs 可能对 AD 发病机制的某些方面具有疾病修饰作用的假设。NSAIDs 不仅可以抑制炎症靶点，从而有助于神经保护，它们还通过尚不清楚的机制减缓淀粉样蛋白沉积。几项针对 AD 患者的 NSAID 治疗的大型临床试验均以失败告终，环氧化酶-2 似乎不是一种用于疾病修饰治疗的有用靶点。然而，在使用萘普生的大型一级预防试验中，可能存在载脂蛋白 E E4 药物基因组学效应和真实但延迟的阳性信号。这鼓励研究人员重新研究 NSAID 有效性的可能机制，这是本综述的主题。
