摘要
背景/目的:阿尔茨海默症是一种复杂的神经退行性疾病,越来越多的证据表明神经性炎症在阿尔茨海默症的致病机理中的重要性。AD患者的脑部会激活补体,并可能会导致局部的炎症状况。许多研究都观察到了AD患者血清第四补体4的过度表达。这个蛋白质有两种亚型,由两种基因编码:位于HLA系 III 区域的C4A和C4B。这些基因抑制了拷贝数变异(CNVs),这种不同的基因拷贝数会影响C4蛋白水平。我们主要研究这两种基因,通过将AD病人和正常对照组的CNVs分布进行对比,来分析它们在AD致病因素的可能相关性。 方法:我们研究了191例AD患者和300例健康对照。C4A与C4B的拷贝数由定量PCR(qPCR)检测。 结果:得到的结果显示与健康对照组进行对比,C4A和C4B的拷贝数在AD患者体内有统计学意义的上升了。(p<0.001) 结论:AD患者体内C4A和C4B高拷贝数的存在可能解释了AD患者体内检测到的C4蛋白的过度表达,因此,突显了C4A和C4B拷贝数变异在发生AD风险中的作用。
关键词: 阿尔茨海默症,补体系统,C4A
Current Alzheimer Research
Title:Complement C4A and C4B Gene Copy Number Study in Alzheimer's Disease Patients
Volume: 14 Issue: 3
Author(s): Michele Zorzetto, Francesca Datturi, Laura Divizia, Cristiana Pistono, Ilaria Campo, Annalisa De Silvestri, Mariaclara Cuccia and Giovanni Ricevuti.
Affiliation:
关键词: 阿尔茨海默症,补体系统,C4A
摘要: Background/Objectives: Increasing evidence suggests the importance of neuroinflammation in the pathogenesis of Alzheimer’s disease (AD), which is a complex neurodegenerative disorder. Complement activation occurs in the brain of patients with AD and seems to contribute to an important local inflammatory state. Increased expression of the fourth serum complement component 4 (C4) has been observed in AD patients in many studies. This protein has two isoforms, encoded by two genes: C4A and C4B localized to the HLA class III region. These genes exhibit copy number variations (CNVs) and this different gene copy number can influence C4 protein levels. We focalized our attention on these two genes, determining the distribution of CNVs in AD patients, compared with healthy controls, in order to analyse their possible involvement in AD pathogenesis.
Methods: We investigated 191 AD patients and 300 healthy controls. The C4A and C4B copy numbers were assessed by quantitative PCR (qPCR).
Results: The results obtained showed a statistically significant increase in the number of copies for both C4A and C4B in AD patients, compared with healthy controls (p<0,001).
Conclusion: The presence of high C4A and C4B copy numbers in AD patients could explain the increased C4 protein expression observed in AD patients, thus highlighting a possible role for C4A and C4B CNVs in the risk of developing AD.
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Michele Zorzetto, Francesca Datturi, Laura Divizia, Cristiana Pistono, Ilaria Campo, Annalisa De Silvestri, Mariaclara Cuccia and Giovanni Ricevuti. , Complement C4A and C4B Gene Copy Number Study in Alzheimer's Disease Patients, Current Alzheimer Research 2017; 14 (3) . https://dx.doi.org/10.2174/1567205013666161013091934
DOI https://dx.doi.org/10.2174/1567205013666161013091934 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
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