用于临床试验富集的脑淀粉样蛋白的血液蛋白预测指标？
Blood protein predictors of brain amyloid for enrichment in clinical trials?
作者信息
Ashton Nicholas J, Kiddle Steven J, Graf John, Ward Malcolm, Baird Alison L, Hye Abdul, Westwood Sarah, Wong Karyuan Vivian, Dobson Richard J, Rabinovici Gil D, Miller Bruce L, Rosen Howard J, Torres Andrew, Zhang Zhanpan, Thurfjell Lennart, Covin Antonia, Hehir Cristina Tan, Baker David, Bazenet Chantal, Lovestone Simon
机构信息
Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley, National Health Service Foundation, London, UK.
Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
出版信息
Alzheimers Dement (Amst). 2015 Mar 29;1(1):48-60. doi: 10.1016/j.dadm.2014.11.005. eCollection 2015 Mar.
BACKGROUND
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.
METHODS
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.
RESULTS
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%.
CONCLUSION
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.
背景
新皮质淀粉样蛋白负荷（NAB）的测量可识别出患阿尔茨海默病（AD）风险显著更高的个体。预测NAB的血液生物标志物对于丰富AD临床试验，包括大规模预防试验，具有很大的实用价值。
方法
对来自澳大利亚衰老成像、生物标志物和生活方式旗舰研究的78名具有一系列NAB值的受试者进行非靶向蛋白质组学发现。通过免疫测定进行技术和独立重复实验。
结果
选择了17个发现候选物进行技术重复。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。在一个独立队列中，FGG血浆水平与年龄相结合预测NAB的敏感性为59%，特异性为78%。
结论
单一血液蛋白FGG与年龄相结合，显示出与NAB相关，因此可能具有丰富临床试验人群的潜力。
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