Alzheimer's Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

中文翻译：

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小胶质细胞在阿尔茨海默氏病中。

阿尔茨海默氏病（AD）是最常见的神经退行性疾病。尽管细胞外淀粉样蛋白-β（Aβ）和细胞内高磷酸化微管相关的tau蛋白聚集体长期以来被确定为AD的特征性神经病理学标志，但针对这些靶标的疾病改良疗法尚未成功。一个新兴的概念是小胶质细胞，即大脑的先天免疫细胞，是AD发病机理的主要参与者。小胶质细胞是长寿的组织驻留专业吞噬细胞，可对其微环境的变化进行调查并快速做出反应。小胶质细胞亚群围绕Aβ斑块聚集，并采用与神经变性特别相关的转录组特征。与小胶质细胞功能和功能障碍相关的大量分子和途径已被确定为介导神经变性的重要参与者。但是，小胶质细胞在AD病理学中发挥有益还是有害作用可能取决于疾病阶段。在这篇综述中，我们总结了有关小胶质细胞在AD中的阶段依赖性作用的当前知识，包括来自遗传和基因表达谱研究以及针对小胶质细胞在人类AD病理学和AD小鼠模型中的新成像技术的最新见解。