阿尔茨海默病外周与中枢神经免疫交互机制及干预策略

Peripheral and central neuroimmune crosstalk in Alzheimer's disease: mechanisms and therapeutic strategies

摘要

阿尔茨海默病（AD）的发病机制复杂，其病理过程涉及全身免疫系统。本文述评了AD病理进程中外周与中枢神经免疫交互的核心机制，重点阐述了血脑屏障破坏与脑膜淋巴管功能障碍如何介导外周免疫细胞向脑内浸润，并与小胶质细胞建立促炎正反馈环路，深入分析了载脂蛋白E4、β2-微球蛋白及髓系细胞触发受体2等关键分子在神经免疫对话中的调节作用。最后，对靶向神经免疫轴的免疫检查点阻断、调节性T细胞回输等新型干预策略进行了展望，旨在为AD的临床精准治疗提供理论依据。

Abstract

Alzheimer's disease (AD) involves complex pathogenic mechanisms and its pathological process implicates an extensive participation of the systemic immune system. This review discussed the core mechanisms of peripheral and central neuroimmune crosstalk in AD progression by highlighting how blood-brain barrier disruption and meningeal lymphatic dysfunction mediated the infiltration of peripheral immune cells into the brain, where they established a pro-inflammatory positive feedback loop with microglia. Furthermore, the regulatory roles of key molecules, including apolipoprotein E4, β2-microglobulin and triggering receptor expressed on myeloid cells 2, in neuroimmune communication were also analyzed. Finally, novel intervention strategies targeting the neuroimmune axis, such as immune checkpoint blockade and regulatory T cell adoptive transfer, were discussed to provide a theoretical basis for clinical precision treatment in AD.

关键词

阿尔茨海默病 / 神经免疫交互 / 血脑屏障 / 外周免疫细胞 / 免疫治疗 / 靶向神经免疫轴

Key words

Alzheimer's disease / neuroimmune crosstalk / blood-brain barrier / peripheral immune cell / immunotherapy / targeting the neuro-immune axis

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基金资助

国家自然科学基金卓越研究群体资助项目B类(82588301)

国家自然科学基金杰出青年基金资助项目(82325018)

国家自然科学基金区域联合基金重点资助项目(U25A2055)

国家自然科学基金面上基金资助项目(82271451)