Alzheimer’s disease (AD) is characterized by extracellular aggregates of amyloid β peptides, intraneuronal tau aggregates, and neuronal death. This pathology triggers activation of microglia. Because variants of genes expressed in microglia correlate with AD risk, microglial response to pathology plausibly impacts disease course. In mouse AD models, single-cell RNA sequencing (scRNA-seq) analyses delineated this response as progressive conversion of homeostatic microglia into disease-associated microglia (DAM); additional reactive microglial populations have been reported in other models of neurodegeneration and neuroinflammation. We review all of these microglial signatures, highlighting four fundamental patterns: DAM, IFN–microglia, MHC-II microglia, and proliferating microglia. We propose that all reported microglia populations are either just one or a combination, depending on the clustering strategy applied and the disease model. We further review single-nucleus RNA sequencing (snRNA-seq) data from human AD specimens and discuss reasons for parallels and discrepancies between human and mouse transcriptional profiles. Finally, we outline future directions for delineating the microglial impact in AD pathogenesis.

中文翻译：

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单细胞水平的阿尔茨海默病中的小胶质细胞。人和老鼠有共同的模式吗？

阿尔茨海默病 (AD) 的特征是淀粉样蛋白 β 肽的细胞外聚集、神经元内 tau 聚集和神经元死亡。这种病理学触发了小胶质细胞的激活。由于小胶质细胞中表达的基因变异与 AD 风险相关，因此小胶质细胞对病理学的反应可能会影响疾病进程。在小鼠 AD 模型中，单细胞 RNA 测序 (scRNA-seq) 分析将这种反应描述为稳态小胶质细胞逐渐转变为疾病相关小胶质细胞 (DAM)。在其他神经变性和神经炎症模型中报告了额外的反应性小胶质细胞群。我们回顾了所有这些小胶质细胞的特征，强调了四种基本模式：DAM、IFN-小胶质细胞、MHC-II 小胶质细胞和增殖小胶质细胞。我们建议所有报告的小胶质细胞群要么只是一个，要么是一个组合，这取决于应用的聚类策略和疾病模型。我们进一步回顾了人类 AD 标本的单核 RNA 测序 (snRNA-seq) 数据，并讨论了人类和小鼠转录谱之间相似和差异的原因。最后，我们概述了描绘 AD 发病机制中小胶质细胞影响的未来方向。