与阿尔茨海默病相关的炎症蛋白被 GLP1 受体激动剂降低：EXSCEL 随机安慰剂对照试验的事后分析。

Inflammatory proteins associated with Alzheimer's disease reduced by a GLP1 receptor agonist: a post hoc analysis of the EXSCEL randomized placebo controlled trial.

机构信息

Department of Psychiatry, Medical Sciences Division, University of Oxford, Oxford, UK.

Duke Center for Precision Health, Duke University School of Medicine, Durham, NC, USA.

出版信息

Alzheimers Res Ther. 2024 Oct 2;16(1):212. doi: 10.1186/s13195-024-01573-x.

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.

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，但这种潜在的疾病修饰作用的机制尚不清楚。我们研究了每周一次艾塞那肽（EQW）对 AD 相关蛋白质组簇的影响。

方法

Exenatide 研究心血管事件降低研究比较了 EQW 2mg 与安慰剂在 13752 例 2 型糖尿病患者中的心血管效应。在 3973 名参与者的基线和 1 年血浆样本中测量了 4979 种蛋白质（Somascan V0.4）。在多变量混合模型中测试了 C 反应蛋白（CRP）、纤维胶凝素-2（FCN2）、纤溶酶原激活物抑制剂 1（PAI-1）、可溶性血管细胞黏附蛋白 1（sVCAM1）和 4 种蛋白质簇。

结果

与安慰剂相比，EQW 显著影响 FCN2（Cohen's d -0.019）、PAI-1（Cohen's d -0.033）、sVCAM-1（Cohen's d 0.035）和细胞因子-细胞因子簇（Cohen's d 0.037）。这些作用在 65 岁以上的个体中持续存在，但在 65 岁以下的个体中不存在。