Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universitat, Erlangen- Nürnberg, Germany.
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, United States.
Curr Alzheimer Res. 2020;17(1):29-43. doi: 10.2174/1567205017666200212155234.
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.
阿尔茨海默病（AD）是最常见的神经退行性疾病。虽然细胞外淀粉样蛋白-β（Aβ）的蛋白聚集物和细胞内过度磷酸化的微管相关tau 一直被认为是 AD 的特征性神经病理学标志，但针对这些靶点的疾病修饰治疗尚未成功。一个新兴的概念是，小胶质细胞，大脑的固有免疫细胞，是 AD 发病机制中的主要参与者。小胶质细胞是寿命长的组织驻留的专业吞噬细胞，可监测并迅速响应其微环境的变化。小胶质细胞亚群聚集在 Aβ斑块周围，并采用与神经退行性变特异性相关的转录组特征。大量与小胶质细胞功能和功能障碍相关的分子和途径已被确定为介导神经退行性变的重要参与者。然而，小胶质细胞在 AD 病理学中是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，我们总结了目前关于小胶质细胞在 AD 中与疾病阶段相关的作用的知识，包括来自遗传和基因表达谱研究的最新见解，以及关注人类 AD 病理学和 AD 小鼠模型中小胶质细胞的新成像技术。
