Alzheimer disease (AD) is the most common neurodegenerative disease, and with no efficient curative treatment available, its medical, social, and economic burdens are expected to dramatically increase. AD is historically characterized by amyloid β (Aβ) plaques and tau neurofibrillary tangles, but over the last 25 years chronic immune activation has been identified as an important factor contributing to AD pathogenesis. In this article, we review recent and important advances in our understanding of the significance of immune activation in the development of AD. We describe how brain-resident macrophages, the microglia, are able to detect Aβ species and be activated, as well as the consequences of activated microglia in AD pathogenesis. We discuss transcriptional changes of microglia in AD, their unique heterogeneity in humans, and emerging strategies to study human microglia. Finally, we expose, beyond Aβ and microglia, the role of peripheral signals and different cell types in immune activation.Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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阿尔茨海默病的免疫激活

阿尔茨海默病（AD）是最常见的神经退行性疾病，由于没有有效的治疗方法，其医疗、社会和经济负担预计将急剧增加。 AD 历史上以 β 淀粉样蛋白 (Aβ) 斑块和 tau 神经原纤维缠结为特征，但在过去 25 年中，慢性免疫激活已被确定为 AD 发病机制的重要因素。在本文中，我们回顾了我们对免疫激活在 AD 发展中的重要性的理解方面的最新重要进展。我们描述了大脑驻留巨噬细胞（小胶质细胞）如何能够检测 Aβ 种类并被激活，以及激活的小胶质细胞在 AD 发病机制中的后果。我们讨论了 AD 中小胶质细胞的转录变化、它们在人类中独特的异质性以及研究人类小胶质细胞的新兴策略。最后，除了 Aβ 和小胶质细胞外，我们还揭示了外周信号和不同细胞类型在免疫激活中的作用。《免疫学年度评论》第 42 卷的预计最终在线出版日期为 2024 年 4 月。请参阅 http://www.annualreviews .org/page/journal/pubdates 了解修订后的估计。