Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, 504 Hamline Street, Grand Forks, ND 58202, USA.
J Neuroimmune Pharmacol. 2009 Dec;4(4):380-8. doi: 10.1007/s11481-009-9165-3. Epub 2009 Aug 11.
A variety of studies have documented increased presence of reactive microglia in the brains of not only Alzheimer's disease (AD) patients but its transgenic mouse models. Since these cells are often characterized in association with fibrillar Abeta peptide-containing plaques, it has been assumed that plaque interaction provides one stimulus for the phenotype observed. The growing appreciation that microglia phenotype changes with age and that resident immune cells are commingled with blood-derived macrophage has complicated understanding of the behavior of these cells in AD. In addition, comparison of microglia within AD brains and the many rodent models suggests that there are population phenotype differences among these cells within any given brain during disease. Recent immunomodulatory strategies that have been employed, although effective at improving behavioral performance, decreasing Abeta plaque load, and altering immune molecule levels, have not yet resolved the details and dynamics of the microglial and macrophage responses. The heterogeneity of microglial presentation in AD brains and its transgenic mouse models and the outcomes of immunoregulatory efforts will be reviewed below along with the remaining question of how much understanding of microglial behavior is actually required in order to propose a microglia-related therapy for AD.
多种研究已经证明，不仅阿尔茨海默病（AD）患者的大脑中存在反应性小胶质细胞增多，而且其转基因小鼠模型也是如此。由于这些细胞通常与含有纤维状 Abeta 肽的斑块相关联，因此人们假设斑块相互作用为观察到的表型提供了一个刺激。人们越来越认识到，小胶质细胞表型随年龄而变化，并且常驻免疫细胞与血液衍生的巨噬细胞混合在一起，这使得人们对 AD 中这些细胞的行为的理解变得复杂。此外，对 AD 大脑中的小胶质细胞与许多啮齿动物模型中的小胶质细胞进行比较表明，在任何给定的疾病大脑中，这些细胞之间存在群体表型差异。最近采用的免疫调节策略虽然在改善行为表现、减少 Abeta 斑块负荷和改变免疫分子水平方面有效，但尚未解决小胶质细胞和巨噬细胞反应的细节和动态。AD 大脑及其转基因小鼠模型中小胶质细胞呈现的异质性以及免疫调节作用的结果将在下面进行综述，同时还存在一个问题，即实际上需要多少了解小胶质细胞行为才能提出针对 AD 的与小胶质细胞相关的治疗方法。
