An estimated 5.7 million Americans suffer from Alzheimer's disease in the United States, with no disease-modifying treatments to prevent or treat cognitive deficits associated with the disease. Genome-wide association studies suggest that an enhancement of clearance mechanisms and/or promotion of an anti-inflammatory response may slow or prevent disease progression. Increasing awareness of distinct roles of complement components in normal brain development and function and in neurodegenerative disorders align with complement-mediated responses, and thus, thorough understanding of these molecular pathways is needed to facilitate successful therapeutic design. Both beneficial and detrimental effects of C1q as well as contributions to local inflammation by C5a–C5aR1 signaling in brain highlight the need for precision of therapeutic design. The potential benefit of β-amyloid clearance from the circulation via CR1-mediated mechanisms is also reviewed. Therapies that suppress inflammation while preserving protective effects of complement could be tested now to slow the progression of this debilitating disease.

中文翻译：

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阿尔茨海默病中补体介导的事件：机制和潜在治疗靶点


据估计，美国有 570 万美国人患有阿尔茨海默病，目前尚无缓解疾病的治疗方法来预防或治疗与该疾病相关的认知缺陷。全基因组关联研究表明，增强清除机制和/或促进抗炎反应可能会减缓或预防疾病进展。人们越来越认识到补体成分在正常大脑发育和功能以及神经退行性疾病中的独特作用与补体介导的反应一致，因此，需要彻底了解这些分子途径以促进成功的治疗设计。 C1q 的有益和有害作用以及大脑中 C5a-C5aR1 信号传导对局部炎症的贡献都凸显了治疗设计精确性的必要性。还回顾了通过 CR1 介导的机制从循环中清除 β-淀粉样蛋白的潜在益处。现在可以测试抑制炎症同时保留补体保护作用的疗法，以减缓这种使人衰弱的疾病的进展。