Chen Hou-Yu, Zhao Yan, Xie Yong-Zhi
Department of Abdominal Surgery, Affiliated Cancer Hospital, Institute of Guangzhou Medical University, Guangdong 510095, China.
Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Rev Neurosci. 2022 Jul 6;34(1):85-101. doi: 10.1515/revneuro-2022-0021. Print 2023 Jan 27.
Most of Alzheimer's disease (AD) cases are sporadic and occur after age 65. With prolonged life expectancy and general population aging, AD is becoming a significant public health concern. The immune system supports brain development, plasticity, and homeostasis, yet it is particularly vulnerable to aging-related changes. Aging of the immune system, called immunosenescence, is the multifaceted remodeling of the immune system during aging. Immunosenescence is a contributing factor to various age-related diseases, including AD. Age-related changes in brain immune cell phenotype and function, crosstalk between immune cells and neural cells, and neuroinflammation work together to promote neurodegeneration and age-related cognitive impairment. Although numerous studies have confirmed the correlation between systemic immune changes and AD, few studies focus on the immune state of brain microenvironment in aging and AD. This review mainly addresses the changes of brain immune microenvironment in aging and AD. Specifically, we delineate how various aspects of the brain immune microenvironment, including immune gateways, immune cells, and molecules, and the interplay between immune cells and neural cells, accelerate AD pathogenesis during aging. We also propose a theoretical framework of therapeutic strategies selectively targeting the different mechanisms to restore brain immune homeostasis.
大多数阿尔茨海默病（AD）病例为散发性，发生在65岁之后。随着预期寿命的延长和人口老龄化，AD正成为一个重大的公共卫生问题。免疫系统支持大脑发育、可塑性和内环境稳定，但它特别容易受到与衰老相关的变化的影响。免疫系统的衰老，即免疫衰老，是衰老过程中免疫系统的多方面重塑。免疫衰老是包括AD在内的各种与年龄相关疾病的一个促成因素。大脑免疫细胞表型和功能的年龄相关变化、免疫细胞与神经细胞之间的相互作用以及神经炎症共同促进神经退行性变和与年龄相关的认知障碍。尽管众多研究已证实全身免疫变化与AD之间存在关联，但很少有研究关注衰老和AD过程中脑微环境的免疫状态。本综述主要探讨衰老和AD过程中脑免疫微环境的变化。具体而言，我们阐述了脑免疫微环境的各个方面，包括免疫通道、免疫细胞和分子，以及免疫细胞与神经细胞之间的相互作用，如何在衰老过程中加速AD的发病机制。我们还提出了一个治疗策略的理论框架，该框架选择性地针对不同机制以恢复脑免疫稳态。
