Mary Arnaud, Mancuso Renzo, Heneka Michael T
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg; email:
Microglia and Inflammation in Neurological Disorders (MIND) Lab, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
Annu Rev Immunol. 2024 Jun;42(1):585-613. doi: 10.1146/annurev-immunol-101921-035222. Epub 2024 Jun 14.
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.
阿尔茨海默病（AD）是最常见的神经退行性疾病，由于目前尚无有效的治愈性治疗方法，其医学、社会和经济负担预计将大幅增加。从历史上看，AD的特征是淀粉样β（Aβ）斑块和tau神经原纤维缠结，但在过去25年中，慢性免疫激活已被确定为导致AD发病机制的一个重要因素。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。我们描述了脑内驻留巨噬细胞——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、它们在人类中的独特异质性以及研究人类小胶质细胞的新兴策略。最后，除了Aβ和小胶质细胞之外，我们还阐述了外周信号和不同细胞类型在免疫激活中的作用。
