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，影响着全世界数百万人。虽然不同的免疫疗法迫在眉睫，但目前只有缓解疾病的药物可用，而且还缺乏治愈方法。在过去十年中，中枢神经系统 (CNS) 的免疫接口及其在神经退行性疾病中的作用受到越来越多的关注。具体而言，新出现的证据表明，循环 CD8 ^+的子集T 细胞穿过脑屏障并与 AD 病理相关。为了更深入地了解适应性免疫系统如何参与疾病发病机制，我们在这里全面概述了 T 细胞对 AD 病理学的贡献，包括脑屏障的变化。此外，我们回顾了通过靶向 T 细胞来对抗 AD 病理和认知衰退来提供这些发现的转化的研究。重要的是，这些数据表明 AD 的免疫变化并不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稳态。