通过 SOMAscan 检测法发现和验证与脑淀粉样蛋白负荷相关的血浆蛋白质组生物标志物。
Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.
机构信息
Department of Psychiatry, University of Oxford, Oxford, UK.
Department of Psychiatry, University of Oxford, Oxford, UK.
出版信息
Alzheimers Dement. 2019 Nov;15(11):1478-1488. doi: 10.1016/j.jalz.2019.06.4951. Epub 2019 Sep 5.
INTRODUCTION
Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins.
METHODS
4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid.
RESULTS
A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization.
DISCUSSION
The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.
简介
血浆蛋白已被广泛研究作为候选生物标志物，以预测脑淀粉样蛋白沉积，从而提高阿尔茨海默病二级预防临床试验的招募效率。大多数此类生物标志物研究针对特定蛋白质，或者偏向于高丰度蛋白质。
方法
在欧洲阿尔茨海默病多模态生物标志物发现研究的医疗信息框架中选择的两组参与者（发现组=516，复制组=365）中测量了 4001 种血浆蛋白，所有参与者均有淀粉样蛋白的测量值。
结果
一组蛋白质（n=44），以及年龄和载脂蛋白 E（APOE）ε4，在发现组（曲线下面积=0.78）和复制组（曲线下面积=0.68）中均表现出良好的预测脑淀粉样蛋白沉积的性能。此外，通过孟德尔随机化证实了淀粉样蛋白和 tau 之间的因果关系。
讨论
研究结果表明，高维血浆蛋白检测可能是一种有用且可重复的测量脑淀粉样蛋白沉积的方法。
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