Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands; Department of Neurobiology and Aging, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Adv Drug Deliv Rev. 2022 Sep;188:114398. doi: 10.1016/j.addr.2022.114398. Epub 2022 Jun 30.
Alzheimer's disease (AD) is the most common form of dementia affecting millions of people worldwide. While different immunotherapies are imminent, currently only disease-modifying medications are available and a cure is lacking. Over the past decade, immunological interfaces of the central nervous system (CNS) and their role in neurodegenerative diseases received increasing attention. Specifically, emerging evidence shows that subsets of circulating CD8 T cells cross the brain barriers and associate with AD pathology. To gain more insight into how the adaptive immune system is involved in disease pathogenesis, we here provide a comprehensive overview of the contribution of T cells to AD pathology, incorporating changes at the brain barriers. In addition, we review studies that provide translation of these findings by targeting T cells to combat AD pathology and cognitive decline. Importantly, these data show that immunological changes in AD are not confined to the CNS and that AD-associated systemic immune changes appear to affect brain homeostasis.
阿尔茨海默病（AD）是最常见的痴呆症形式，影响着全球数以百万计的人。虽然有许多不同的免疫疗法即将出现，但目前仅有的是能够改变疾病进程的药物，而缺乏治愈方法。在过去的十年中，中枢神经系统（CNS）的免疫学界面及其在神经退行性疾病中的作用受到了越来越多的关注。具体来说，新出现的证据表明，循环 CD8 T 细胞亚群可以穿过血脑屏障，并与 AD 病理学相关联。为了更深入地了解适应性免疫系统如何参与疾病的发病机制，我们在这里全面概述了 T 细胞对 AD 病理学的贡献，包括对血脑屏障的改变。此外，我们还回顾了通过针对 T 细胞来对抗 AD 病理学和认知能力下降的这些发现的转化研究。重要的是，这些数据表明，AD 中的免疫学变化不仅局限于中枢神经系统，而且与 AD 相关的全身免疫变化似乎会影响大脑的内稳态。
