A double-edged sword: Exploring the neuroprotective/damaging mechanisms of complement activation in Alzheimer's disease

IF 2.7

Aging and health research Pub Date : 2025-12-01 Epub Date: 2025-11-20 DOI:10.1016/j.ahr.2025.100267

Jie Wang , Jie Wu , Xiaoxi Ma , Yuhan Wu , Zhenxu Xiao , Xiaowen Zhou , Ding Ding , Qian-hua Zhao

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Abstract

Background

Alzheimer's disease (AD), the most widespread neurodegenerative disorder afflicting older adults, is characterized by a progressive decline in cognitive function, behavior, and social skills. The complement system, a cornerstone of the innate immune system, plays a crucial role in rapidly recognizing and clearing foreign pathogens, damaged cells, and cellular debris. Recently, there has been growing interest in understanding the intricate roles of complement components in both normal brain development and neurodegenerative processes.

Methods

We reviewed the activation and role of the complement system in AD, specifically highlighting its stage-dependent functional duality, including both protective and detrimental roles. Furthermore, we assessed current and promising therapeutic strategies targeting complement components in AD.

Results

The early stage, defined by pre-plaque pathology, was dominated by protective clearance mechanisms, while the progressive phase, characterized by widespread amyloid and tau pathology, exhibited detrimental neuroinflammation and synaptic loss.

Conclusions

Understanding the dual roles of the complement system in AD is crucial for developing targeted therapies.

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双刃剑：探索补体激活在阿尔茨海默病中的神经保护/损伤机制

背景：阿尔茨海默病（AD）是困扰老年人的最普遍的神经退行性疾病，其特征是认知功能、行为和社交技能的进行性下降。补体系统是先天免疫系统的基石，在快速识别和清除外来病原体、受损细胞和细胞碎片方面起着至关重要的作用。最近，人们对补体成分在正常大脑发育和神经退行性过程中的复杂作用越来越感兴趣。我们回顾了补体系统在AD中的激活和作用，特别强调了它的阶段依赖性功能，包括保护和有害作用。此外，我们评估了针对补体成分治疗AD的当前和有希望的治疗策略。结果斑块前病理定义的早期以保护性清除机制为主，而以广泛的淀粉样蛋白和tau病理为特征的进展期表现出有害的神经炎症和突触丧失。结论了解补体系统在AD中的双重作用对开发靶向治疗具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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