{"title":"Immune Activation in Alzheimer Disease.","authors":"Arnaud Mary, Renzo Mancuso, Michael T Heneka","doi":"10.1146/annurev-immunol-101921-035222","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-immunol-101921-035222","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/14 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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,由于没有有效的治疗方法,预计其医疗、社会和经济负担将急剧增加。淀粉样β(Aβ)斑块和tau神经纤维缠结是阿尔茨海默病的历史特征,但在过去的25年中,慢性免疫激活已被确定为导致阿尔茨海默病发病的一个重要因素。在这篇文章中,我们回顾了最近在理解免疫激活在AD发病中的意义方面取得的重要进展。我们描述了大脑驻留的巨噬细胞--小胶质细胞如何能够检测到 Aβ 物种并被激活,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。免疫学年刊》(Annual Review of Immunology)第42卷的最终在线出版日期预计为2024年4月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
期刊介绍:
The Annual Review of Immunology, in publication since 1983, focuses on basic immune mechanisms and molecular basis of immune diseases in humans. Topics include innate and adaptive immunity; immune cell development and differentiation; immune control of pathogens (viruses, bacteria, parasites) and cancer; and human immunodeficiency and autoimmune diseases. The current volume of this journal has been converted from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.