Daskoulidou Nikoleta, Carpanini Sarah M, Zelek Wioleta M, Morgan B Paul
UK Dementia Research Institute Cardiff, Cardiff University, Cardiff, UK.
Curr Top Behav Neurosci. 2025;69:3-24. doi: 10.1007/7854_2024_524.
Complement is a critical component of innate immunity, evolved to defend against pathogens and clear toxic debris ranging from dead and dying cells to immune complexes. These roles make complement a key player in homeostasis; however, complement has a dark side. When the rigid control mechanisms fail, complement becomes dysregulated, acting as a driver of inflammation and resultant pathology in numerous diseases. Roles of complement in Alzheimer's disease (AD) and other dementias have emerged in recent years, supported by genetic, biomarker and pathological evidence and animal model studies. Numerous questions remain regarding the precise roles of complement in the brain in health and disease, including where and when complement is expressed, how it contributes to immune defence and garbage disposal in the healthy brain, and exactly how complement contributes to pathology in dementias. In this brief review, we will summarise current knowledge on complement roles in brain, present the evidence implicating complement in AD and explore whether complement represents an attractive therapeutic target for AD.
补体是先天免疫的关键组成部分，其进化目的是抵御病原体并清除从死亡和濒死细胞到免疫复合物等各种有毒碎片。这些作用使补体成为体内平衡的关键因素；然而，补体也有不利的一面。当严格的控制机制失效时，补体就会失调，在许多疾病中成为炎症和由此导致的病理状态的驱动因素。近年来，补体在阿尔茨海默病（AD）和其他痴呆症中的作用逐渐显现，这得到了遗传学、生物标志物、病理学证据以及动物模型研究的支持。关于补体在大脑健康和疾病中的精确作用，仍有许多问题，包括补体在何处以及何时表达、它如何在健康大脑中促进免疫防御和垃圾处理，以及补体究竟如何导致痴呆症中的病理状态。在这篇简短的综述中，我们将总结关于补体在大脑中作用的现有知识，展示补体与AD相关的证据，并探讨补体是否是AD有吸引力的治疗靶点。
