Department of Microbiology and Immunology, University of Illinois College of Medicine, 835 S Wolcott street, MC 790, Chicago, Chicago, IL 60612, United States.
Department of Anatomy and Cell Biology, University of Illinois College of Medicine, 808 S Wood street, MC 512, Chicago, Chicago, IL 60612, United States.
J Leukoc Biol. 2024 Nov 27;116(6):1269-1290. doi: 10.1093/jleuko/qiae134.
Progressive memory loss and cognitive dysfunction, encompassing deficits in learning, memory, problem solving, spatial reasoning, and verbal expression, are characteristics of Alzheimer's disease and related dementia. A wealth of studies has described multiple roles of the immune system in the development or exacerbation of dementia. Individuals with autoimmune disorders can also develop cognitive dysfunction, a phenomenon termed "autoimmune dementia." Together, these findings underscore the pivotal role of the neuroimmune axis in both Alzheimer's disease and related dementia and autoimmune dementia. The dynamic interplay between adaptive and innate immunity, both in and outside the brain, significantly affects the etiology and progression of these conditions. Multidisciplinary research shows that cognitive dysfunction arises from a bidirectional relationship between the nervous and immune systems, though the specific mechanisms that drive cognitive impairments are not fully understood. Intriguingly, this reciprocal regulation occurs at multiple levels, where neuronal signals can modulate immune responses, and immune system-related processes can influence neuronal viability and function. In this review, we consider the implications of autoimmune responses in various autoimmune disorders and Alzheimer's disease and explore their effects on brain function. We also discuss the diverse cellular and molecular crosstalk between the brain and the immune system, as they may shed light on potential triggers of peripheral inflammation, their effect on the integrity of the blood-brain barrier, and brain function. Additionally, we assess challenges and possibilities associated with developing immune-based therapies for the treatment of cognitive decline.
进行性记忆丧失和认知功能障碍，包括学习、记忆、解决问题、空间推理和语言表达方面的缺陷，是阿尔茨海默病和相关痴呆的特征。大量研究描述了免疫系统在痴呆的发展或恶化中的多种作用。自身免疫性疾病患者也可能出现认知功能障碍，这种现象称为“自身免疫性痴呆”。这些发现共同强调了神经免疫轴在阿尔茨海默病和相关痴呆以及自身免疫性痴呆中的关键作用。适应性免疫和固有免疫在大脑内外的动态相互作用，显著影响这些疾病的病因和进展。多学科研究表明，认知功能障碍源于神经系统和免疫系统之间的双向关系，尽管驱动认知障碍的具体机制尚不完全清楚。有趣的是，这种相互调节发生在多个层面，其中神经元信号可以调节免疫反应，而免疫系统相关过程可以影响神经元的存活和功能。在这篇综述中，我们考虑了各种自身免疫性疾病和阿尔茨海默病中自身免疫反应的意义，并探讨了它们对大脑功能的影响。我们还讨论了大脑和免疫系统之间多样化的细胞和分子串扰，因为它们可能揭示潜在的外周炎症触发因素、它们对血脑屏障完整性的影响以及大脑功能。此外，我们评估了开发针对认知衰退的免疫疗法的挑战和可能性。
