Boche Delphine, Nicoll James A R
Division of Clinical Neurosciences, University of Southampton, Southampton, UK.
Brain Pathol. 2008 Apr;18(2):267-78. doi: 10.1111/j.1750-3639.2008.00134.x.
In Alzheimer's disease (AD), there is abnormal accumulation of Abeta and tau proteins in the brain. There is an associated immunological response, but it is still unclear whether this is beneficial or harmful. Inflammation in AD, specifically in the form of microglial activation, has, for many years, been considered to contribute to disease progression. However, two types of evidence suggest that it may be appropriate to revise this view: first, the disappointing results of prospective clinical trials of anti-inflammatory agents and, second, the observation that microglia can clear plaques in AD following Abeta immunization. Although Abeta immunization alters AD pathology, there is limited evidence so far of benefit to cognitive function. Immunization against microorganisms is almost always used as a method of disease prevention rather than to treat a disease process that has already started. In animal models, immunotherapy at an early age can protect against Abeta accumulation and it will be interesting to see if this can usefully be applied to humans to prevent AD.
在阿尔茨海默病(AD)中,大脑中β淀粉样蛋白(Aβ)和tau蛋白会异常积聚。存在相关的免疫反应,但尚不清楚这是有益还是有害。多年来,AD中的炎症,特别是小胶质细胞激活形式,一直被认为会促进疾病进展。然而,两类证据表明可能需要修正这一观点:第一,抗炎药物前瞻性临床试验的令人失望的结果;第二,观察到在Aβ免疫后小胶质细胞可以清除AD中的斑块。尽管Aβ免疫改变了AD病理,但迄今为止对认知功能有益的证据有限。针对微生物的免疫几乎总是用作疾病预防方法,而非用于治疗已经开始的疾病进程。在动物模型中,幼年时进行免疫治疗可以预防Aβ积聚,看看这是否能有效地应用于人类以预防AD将会很有意思。