Blood protein predictors of brain amyloid for enrichment in clinical trials?
Blood protein predictors of brain amyloid for enrichment in clinical trials?
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DOI：
10.1016/j.dadm.2014.11.005
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发表时间：
2015-03
期刊：
影响因子：
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通讯作者：
AIBL Research Group
中科院分区：
文献类型：
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作者：
Ashton NJ;Kiddle SJ;Graf J;Ward M;Baird AL;Hye A;Westwood S;Wong KV;Dobson RJ;Rabinovici GD;Miller BL;Rosen HJ;Torres A;Zhang Z;Thurfjell L;Covin A;Hehir CT;Baker D;Bazenet C;Lovestone S;AIBL Research Group
新皮质淀粉样蛋白负荷（NAB）的措施，确定个人谁是在发展阿尔茨海默氏病（AD）的风险大大增加。基于血液的生物标志物预测NAB将对丰富AD临床试验，包括大规模预防试验具有很大的实用性。非靶向蛋白质组学发现应用于来自澳大利亚成像，生物标志物和生活方式衰老旗舰研究的78名受试者，具有一系列NAB值。通过免疫测定进行技术和独立重复。17个发现候选者被选中进行技术复制。已证实α2-巨球蛋白、纤维蛋白原γ链（FGG）和补体因子H相关蛋白1与NAB相关。在一个独立的队列中，FGG血浆水平结合年龄预测NAB的敏感性为59%，特异性为78%。单一的血液蛋白FGG与年龄相结合，显示与NAB相关，因此可能具有富集临床试验人群的潜力。
Measures of neocortical amyloid burden (NAB) identify individuals who are at substantially greater risk of developing Alzheimer's disease (AD). Blood-based biomarkers predicting NAB would have great utility for the enrichment of AD clinical trials, including large-scale prevention trials. Nontargeted proteomic discovery was applied to 78 subjects from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing with a range of NAB values. Technical and independent replications were performed by immunoassay. Seventeen discovery candidates were selected for technical replication. α2-Macroglobulin, fibrinogen γ-chain (FGG), and complement factor H-related protein 1 were confirmed to be associated with NAB. In an independent cohort, FGG plasma levels combined with age predicted NAB had a sensitivity of 59% and specificity of 78%. A single blood protein, FGG, combined with age, was shown to relate to NAB and therefore could have potential for enrichment of clinical trial populations.