Ivan Koychev, Graham Reid, Maggie Nguyen, Robert J Mentz, Dan Joyce, Svati H Shah, Rury R Holman
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引用次数: 0
摘要
背景：胰高血糖素样肽-1受体激动剂是预防阿尔茨海默病（AD）的可行选择，但这种潜在的疾病调节作用的机制尚不清楚。我们研究了每周一次的艾塞那肽（EQW）对与阿尔茨海默病相关的蛋白质组群的影响：艾塞那肽降低心血管事件研究比较了 EQW 2 毫克与安慰剂对 13,752 名 2 型糖尿病患者心血管的影响。对 3,973 名参与者的基线和 1 年血浆样本中的 4,979 种蛋白质进行了测量（Somascan V0.4）。在多变量混合模型中对 C 反应蛋白 (CRP)、ficolin-2 (FCN2)、纤溶酶原激活物抑制剂 1 (PAI-1)、可溶性血管细胞粘附蛋白 1 (sVCAM1) 和 4 组蛋白质进行了测试：与安慰剂相比，EQW 对 FCN2（Cohen's d -0.019）、PAI-1（Cohen's d -0.033）、sVCAM-1（Cohen's d 0.035）和一个细胞因子-细胞因子群（Cohen's d 0.037）有显著影响。这些效果在 65 岁以上的人群中持续存在，但在 65 岁以下的人群中则没有：结论：EQW治疗与AD相关炎症蛋白的显著变化有关：EXSCEL已在ClinicalTrials.gov上注册：试验注册：EXSCEL 于 2010 年 6 月 10 日在 ClinicalTrials.gov 上注册：NCT01144338。
Inflammatory proteins associated with Alzheimer's disease reduced by a GLP1 receptor agonist: a post hoc analysis of the EXSCEL randomized placebo controlled trial.
Background: Glucagon-like peptide-1 receptor agonists are a viable option for the prevention of Alzheimer's disease (AD) but the mechanisms of this potential disease modifying action are unclear. We investigated the effects of once-weekly exenatide (EQW) on AD associated proteomic clusters.
Methods: The Exenatide Study of Cardiovascular Event Lowering study compared the cardiovascular effects of EQW 2 mg with placebo in 13,752 people with type 2 diabetes mellitus. 4,979 proteins were measured (Somascan V0.4) on baseline and 1-year plasma samples of 3,973 participants. C-reactive protein (CRP), ficolin-2 (FCN2), plasminogen activator inhibitor 1 (PAI-1), soluble vascular cell adhesion protein 1 (sVCAM1) and 4 protein clusters were tested in multivariable mixed models.
Results: EQW affected FCN2 (Cohen's d -0.019), PAI-1 (Cohen's d -0.033), sVCAM-1 (Cohen's d 0.035) and a cytokine-cytokine cluster (Cohen's d 0.037) significantly compared with placebo. These effects were sustained in individuals over the age of 65 but not in those under 65.
Conclusions: EQW treatment was associated with significant change in inflammatory proteins associated with AD.
Trial registration: EXSCEL is registered on ClinicalTrials.gov: NCT01144338 on 10th of June 2010.
期刊介绍：
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
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