Department of Neurology & National Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Ageing Res Rev. 2021 Sep;70:101409. doi: 10.1016/j.arr.2021.101409. Epub 2021 Jul 14.
Alzheimer's disease (AD) is the most common neurodegenerative disorder where the accumulation of amyloid plaques and the formation of tau tangles are the prominent pathological hallmarks. Increasing preclinical and clinical studies have revealed that different components of the immune system may act as important contributors to AD etiology and pathogenesis. The recognition of misfolded Aβ and tau by immune cells can trigger a series of complex immune responses in AD, and then lead to neuroinflammation and neurodegeneration. In parallel, genome-wide association studies have also identified several immune related loci associated with increased - risk of AD by interfering with the function of immune cells. Other immune related factors, such as impaired immunometabolism, defective meningeal lymphatic vessels and autoimmunity might also be involved in the pathogenesis of AD. Here, we review the data showing the alterations of immune cells in the AD trajectory and seek to demonstrate the crosstalk between the immune cell dysfunction and AD pathology. We then discuss the most relevant research findings in regards to the influences of gene susceptibility of immune cells for AD. We also consider impaired meningeal lymphatics, immunometabolism and autoimmune mechanisms in AD. In addition, immune related biomarkers and immunotherapies for AD are also mentioned in order to offer novel insights for future research.
阿尔茨海默病（AD）是最常见的神经退行性疾病，其中淀粉样斑块的积累和tau 缠结的形成是突出的病理学特征。越来越多的临床前和临床研究表明，免疫系统的不同成分可能是 AD 病因和发病机制的重要贡献者。免疫细胞识别错误折叠的 Aβ 和 tau 可以在 AD 中引发一系列复杂的免疫反应，进而导致神经炎症和神经变性。与此同时，全基因组关联研究也发现了几个与免疫细胞功能障碍相关的免疫相关基因座，这些基因座通过干扰免疫细胞的功能增加了 AD 的风险。其他免疫相关因素，如免疫代谢受损、脑膜淋巴管缺陷和自身免疫，也可能参与 AD 的发病机制。在这里，我们回顾了显示 AD 轨迹中免疫细胞改变的数据，并试图展示免疫细胞功能障碍与 AD 病理学之间的相互作用。然后，我们讨论了与免疫细胞基因易感性对 AD 的影响有关的最相关的研究结果。我们还考虑了 AD 中的脑膜淋巴管、免疫代谢和自身免疫机制受损的情况。此外，还提到了与 AD 相关的免疫相关生物标志物和免疫疗法，以期为未来的研究提供新的见解。
