Complement receptor 1 (CR1) and Alzheimer's disease
Complement receptor 1 (CR1) and Alzheimer's disease
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DOI：
10.1016/j.imbio.2011.07.017
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发表时间：
2012-02-01
期刊：
影响因子：
2.8
通讯作者：
Hardy, John
中科院分区：
文献类型：
--
作者：
Crehan, Helen;Holton, Patrick;Hardy, John
阿尔茨海默病（Alzheimer's disease，AD）是最常见的神经退行性疾病，给老年人带来了日益沉重的负担。已经鉴定了负责罕见的常染色体显性形式的AD的几个基因座（APP、PS1和PS2），并且这些基因座促进了AD病因学的淀粉样蛋白级联假说的发展。晚发性痴呆（LOAD）的遗传学定义不明确，直到最近，唯一已知的危险因素是APOE的等位基因。最近的全基因组关联研究（GWAS）已经确定了增加LOAD风险的常见遗传变异。在这些研究中强调的两个基因，CLU和CR1，表明补体系统在AD病因学中的作用。在这篇综述中，我们分析的证据参与补体在AD。特别是，我们专注于一个基因，CR1，及其在补体级联反应中的作用。CR1是补体片段C3b和C4b的受体，并在许多不同的细胞类型上表达，特别是在循环系统中。我们着眼于基因多态性的证据，以及这些有据可查的变化可能产生的生理效应。最后，我们讨论了CR1基因多态性与AD的淀粉样蛋白级联假说的可能影响，以及CR1可能导致AD发病的方式。(C)2011年Elsevier GmbH。All rights reserved.
Alzheimer's disease (AD) is the most common neurodegenerative disease and it poses an ever-increasing burden to an aging population. Several loci responsible for the rare, autosomal dominant form of AD have been identified (APP, PS1 and PS2), and these have facilitated the development of the amyloid cascade hypothesis of AD aetiology. The late onset form of the disease (LOAD) is poorly defined genetically, and up until recently the only known risk factor was the epsilon 4 allele of APOE. Recent genome-wide association studies (GWAS) have identified common genetic variants that increase risk of LOAD. Two of the genes highlighted in these studies, CLU and CR1, suggest a role for the complement system in the aetiology of AD. In this review we analyse the evidence for an involvement of complement in AD. In particular we focus on one gene, CR1, and its role in the complement cascade. CR1 is a receptor for the complement fragments C3b and C4b and is expressed on many different cell types, particularly in the circulatory system. We look at the evidence for genetic polymorphisms in the gene and the possible physiological effects of these well-documented changes. Finally, we discuss the possible impact of CR1 genetic polymorphisms in relation to the amyloid cascade hypothesis of AD and the way in which CR1 may lead to AD pathogenesis. (C) 2011 Elsevier GmbH. All rights reserved.