McGill University Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
Trends Pharmacol Sci. 2017 Nov;38(11):956-966. doi: 10.1016/j.tips.2017.07.005. Epub 2017 Aug 31.
In 1990 it was reported that individuals receiving NSAIDs (non-steroidal anti-inflammatory drugs) showed a markedly reduced prevalence of Alzheimer's disease (AD) compared to the overall population. Large epidemiological studies corroborated this assertion and provoked numerous prospective AD clinical trials with a variety of NSAIDs, all of which demonstrated lack of efficacy. It is postulated that the explanation for the success of NSAIDS in preventing AD onset when given at preclinical stages, and for their failure when administered after AD clinical presentation, lies in the changing nature of central nervous system (CNS) inflammation in the decades-long continuum of AD pathology. Early disease-aggravating CNS inflammation might start decades before the presentation of severe cognitive impairments or dementia, and the nature of this process will co-evolve with the neuropathological progression from preclinical to clinical AD stages. This early CNS inflammation should be considered a promising therapeutic target as we continue searching for an unequivocal diagnosis of AD preclinical stages.
1990 年有报道称，与普通人群相比，服用非甾体抗炎药 (NSAIDs) 的个体患阿尔茨海默病 (AD) 的患病率明显降低。大型流行病学研究证实了这一说法，并引发了多项针对各种 NSAIDs 的前瞻性 AD 临床试验，所有这些试验均表明其无效。据推测，NSAIDs 在临床前阶段预防 AD 发病时取得成功，而在 AD 临床发病后给予 NSAIDs 时却失败的原因，在于 AD 病理数十年连续过程中中枢神经系统 (CNS) 炎症性质的变化。早期加重疾病的 CNS 炎症可能在严重认知障碍或痴呆出现前数十年就开始了，而这一过程的性质将与从临床前到临床 AD 阶段的神经病理学进展共同演变。由于我们继续寻找 AD 临床前阶段明确的诊断方法，因此应将这种早期的 CNS 炎症视为有前途的治疗靶点。
