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Early and Late CNS Inflammation in Alzheimer’s Disease: Two Extremes of a Continuum?
Trends in Pharmacological Sciences ( IF 13.9 ) Pub Date : 2017-08-31 , DOI: 10.1016/j.tips.2017.07.005
A. Claudio Cuello

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.



中文翻译:

阿尔茨海默氏病中的中枢神经系统早期和晚期炎症:连续性的两个极端?

1990年,据报道,与总人口相比,接受NSAID(非甾体类抗炎药)治疗的人的阿尔茨海默氏病(AD)患病率明显降低。大规模的流行病学研究证实了这一主张,并引发了使用多种NSAID进行的众多前瞻性AD临床试验,所有这些都证明缺乏疗效。据推测,NSAIDS在临床前阶段成功预防AD发病以及在AD临床表现后给予AD失败的解释取决于数十年来中枢神经系统(CNS)炎症的变化性质。 AD病理学的连续体。在严重认知功能障碍或痴呆症出现之前的数十年中,可能会加剧疾病的早期中枢神经系统炎症,并且该过程的性质将与从临床前阶段到临床AD阶段的神经病理学发展共同发展。随着我们继续寻找对AD临床前阶段的明确诊断,这种早期的CNS炎症应被视为有希望的治疗靶点。

更新日期:2017-08-31
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