Guymer Robyn, Cipriani Tania, Rittenhouse Kay D, Lim Lyndell, Robman Liubov D, Li Wenlin, Wang Wenlian, Deng Shibing, Banerjee Poulabi
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia,
Graefes Arch Clin Exp Ophthalmol. 2015 Aug;253(8):1347-54. doi: 10.1007/s00417-015-2970-x. Epub 2015 Mar 7.
To investigate the plasma levels of amyloid beta (Aβ) and select inflammatory mediators in patients with various stages of AMD compared to that of age-matched controls, and discern a relationship to disease severity.
Plasma samples were obtained from AMD subjects at various stages of disease-early (drusen only), geographic atrophy (GA), neovascular AMD (CNV)-and from controls of similar age without AMD. Samples were analyzed using a commercially available ELISA kit (sixteen cytokines) or LC/MS/MS (Aβ isotypes). Descriptive statistics were compiled on all analytes. Analysis of covariance (ANCOVA) was conducted to compare each analyte across AMD groups while adjusting for sex and age of the patients, and in comparison to the control group. Receiver operating characteristics plots were generated for the strongest predictor variables.
Levels of alternative spliced CC3 proteins were significantly different between controls and CNV groups (p < 0.05), with median levels almost twice higher in CNV than in controls. There was an increasing trend for plasma levels of Αβ isotypes across AMD progressive stages (p values ranged from 0.052 to 0.0012) (ANCOVA). When adjusted for multiple comparisons analysis, plasma Aβ 1-42 levels, and its ratio with Aβ 1-40 were the most significantly associated with late AMD stages. Consistently with the ANCOVA results for Αβ isotypes, the ROC curve showed a moderate prediction (AUC = - ~ 0.78) of AMD vs control using the Aβ 1-42 isotype.
Plasma Aβ 1-42 may have utility as a systemic biomarker for AMD.
研究不同阶段年龄相关性黄斑变性（AMD）患者与年龄匹配的对照组相比，血浆中β淀粉样蛋白（Aβ）水平及多种炎症介质水平，并探讨其与疾病严重程度的关系。
采集处于疾病不同阶段（早期仅存在玻璃膜疣、地图样萎缩（GA）、新生血管性AMD（CNV））的AMD患者以及年龄相仿无AMD的对照者的血浆样本。使用市售酶联免疫吸附测定试剂盒（检测16种细胞因子）或液相色谱/串联质谱法（检测Aβ亚型）对样本进行分析。对所有分析物进行描述性统计。进行协方差分析（ANCOVA），在调整患者性别和年龄的同时，比较AMD各亚组的每种分析物，并与对照组进行比较。针对最强预测变量绘制受试者工作特征曲线。
对照组与CNV组之间可变剪接CC3蛋白水平存在显著差异（p < 0.05），CNV组的中位数水平几乎是对照组的两倍。在AMD进展阶段，Aβ亚型的血浆水平呈上升趋势（p值范围为0.052至0.0012）（ANCOVA）。经过多重比较分析调整后，血浆Aβ 1-42水平及其与Aβ 1-40的比值与晚期AMD阶段的相关性最为显著。与Aβ亚型的ANCOVA结果一致，ROC曲线显示使用Aβ 1-42亚型对AMD与对照进行预测具有中等效果（曲线下面积（AUC）约为0.78）。
血浆Aβ 1-42可能作为AMD的一种全身性生物标志物。
