阿尔茨海默病进展的预后多肽血浆生物标志物。
Prognostic polypeptide blood plasma biomarkers of Alzheimer's disease progression.
机构信息
Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Department of Neurology, School of Medicine, University of Eastern Finland, Kuopio, Finland.
出版信息
J Alzheimers Dis. 2014;40(3):659-66. doi: 10.3233/JAD-132102.
BACKGROUND
Patients with mild cognitive impairment (MCI) have varying risks of progression to Alzheimer's disease (AD).
OBJECTIVE
To test the utility of the relative abundances of blood plasma polypeptides for predicting the risk of AD progression.
METHODS
119 blood plasma samples of patients with MCI with different outcomes (stable MCI and progressive MCI) were analyzed by untargeted, label-free shotgun proteomics. Predictive biomarkers of progressive MCI were selected by multivariate analysis, followed by cross-validation of the predictive model.
RESULTS
The best model demonstrated the accuracy of ca. 79% in predicting progressive MCI. Sex differences of the predictive biomarkers were also assessed. We have identified some sex-specific protein biomarkers, e.g., alpha-2-macrogloblin (A2M), which strongly correlates with female AD progression but not with males.
CONCLUSION
Significant sex bias in AD-specific biomarkers underscores the necessity of selecting sex-balanced cohort in AD biomarker studies, or using sex-specific models. Blood protein biomarkers are found to be promising for predicting AD progression in clinical settings.
背景
轻度认知障碍（MCI）患者向阿尔茨海默病（AD）进展的风险各不相同。
目的
测试血浆多肽相对丰度预测 AD 进展风险的效用。
方法
通过无标记、无靶向的鸟枪法蛋白质组学分析了具有不同结局（稳定 MCI 和进展性 MCI）的 119 例 MCI 患者的血浆样本。通过多元分析选择进展性 MCI 的预测生物标志物，然后对预测模型进行交叉验证。
结果
最佳模型预测进展性 MCI 的准确率约为 79%。还评估了预测生物标志物的性别差异。我们已经确定了一些性别特异性蛋白生物标志物，例如α-2-巨球蛋白（A2M），它与女性 AD 进展密切相关，但与男性无关。
结论
AD 特异性生物标志物存在显著的性别偏见，这突出表明在 AD 生物标志物研究中需要选择性别均衡的队列，或使用性别特异性模型。血液蛋白生物标志物有望在临床环境中预测 AD 的进展。
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