Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion of MCI
Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion of MCI
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DOI：
10.1212/01.wnl.0000286944.22262.ff
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发表时间：
2007-12-11
期刊：
影响因子：
9.9
通讯作者：
Hampel, H.
中科院分区：
文献类型：
--
作者：
Ewers, M.;Buerger, K.;Hampel, H.
背景：脑脊液中过度磷酸化tau(p-tau)的测定被认为是预测轻度认知障碍(MCI)患者阿尔茨海默病(AD)的候选生物标志物。目的：在一项多中心研究中，评估先验定义的苏氨酸231位tau磷酸化标准(p-tau(231))预测MCI向AD转变的准确性。方法：该研究包括43名MCI转换者、45名稳定的MCI(平均随访间隔为1.5年)和57名健康对照(仅在基线时)。受试者在四个国际专家站点进行了回顾性研究设计。用COX回归模型对转归状态进行预测。结果：p-tau水平是转换的显著预测因子(B=0.026，p=0.001)，与年龄、性别、简易智力状态检查和载脂蛋白E基因无关。对于预先确定的临界点(27.32pg/ml)，各中心间的敏感性介于66.7~100%，特异性介于66.7~77.8%。正确率为79.95%(95%CI=79.9~80.00%)。后自组织定义的分界值的平均自举分类准确率为80.45%(95%CI=80.24~80.76%)。结论：先验定义的分界值p-tau(231)跨中心产生相对稳定的结果，提示以p-tau(231)为标准标准预测阿尔茨海默病是一种良好的可行性。
Background: The measurement of hyperphosphorylated tau (p-tau) in CSF has been proposed as a biomarker candidate for the prediction of Alzheimer disease ( AD) in patients with mild cognitive impairment (MCI). However, a standard quantitative criterion of p-tau has not been evaluated.Objective: To assess in a multicenter study the predictive accuracy of an a priori defined criterion of tau phosphorylated at threonine 231 (p-tau(231)) for the prediction of conversion from MCI to AD during a short-term observation interval.Methods: The study included 43 MCI converters, 45 stable MCI (average follow-up interval = 1.5 years), and 57 healthy controls ( at baseline only). Subjects were recruited at four international expert sites in a retrospective study design. Cox regression models stratified according to center were used to predict conversion status. Bootstrapped 95% CIs of classification accuracy were computed.Results: Levels of p-tau(231) were a significant predictor of conversion (B = 0.026, p = 0.001), independent of age, gender, Mini-Mental State Examination, and ApoE genotype. For an a priori defined cutoff point (27.32 pg/mL), sensitivity ranged between 66.7 and 100% and specificity between 66.7 and 77.8% among centers. The bootstrapped mean percentage of correctly classified cases was 79.95% (95% Cl = 79.9 to 80.00%). Post hoc defined cutoff values yielded a mean bootstrapped classification accuracy of 80.45% (95% Cl = 80.24 to 80.76%).Conclusions: An a priori defined cutoff value of p-tau(231) yields relatively stable results across centers, suggesting a good feasibility of a standard criterion of p-tau(231) for the prediction of Alzheimer disease.