Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people.
Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people.
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DOI：
10.1001/archneurol.2010.179
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发表时间：
2010-08
影响因子：
--
通讯作者：
Trojanowski, John Q.
中科院分区：
文献类型：
--
作者：
De Meyer, Geert;Shapiro, Fred;Vanderstichele, Hugo;Vanmechelen, Eugeen;Engelborghs, Sebastiaan;De Deyn, Peter Paul;Coart, Els;Hansson, Oskar;Minthon, Lennart;Zetterberg, Henrik;Blennow, Kaj;Shaw, Leslie;Trojanowski, John Q.
在不使用临床诊断信息的情况下，以独立、无监督的方式识别阿尔茨海默病（AD）的典型生物标志物模式。混合建模方法。阿尔茨海默病神经影像学倡议数据库。认知正常人群，AD患者，轻度认知障碍个体。脑脊液来源的β-淀粉样蛋白1-42、总tau蛋白和磷酸化tau181P蛋白浓度被用作临床特征良好的数据集的生物标志物。在另外2个数据集上验证了资格分析的结果，其中1个数据集是尸检证实的。利用美国阿尔茨海默病神经影像学倡议数据集，脑脊液β-淀粉样蛋白1 - 42/磷酸化tau181P生物标志物混合物模型确定了与AD相关的1个特征，而另一个与“健康”状态相匹配。在AD组、轻度认知障碍组和认知正常组中，分别有90%、72%和36%的患者存在AD特征。AD特征认知正常组载脂蛋白E ε4等位基因携带者较多。结果在另外2个数据集上得到验证。在一项由68例尸检证实的AD病例组成的研究中，68例患者中有64例（94%的敏感性）被正确分类为AD特征。在另一组随访5年的轻度认知障碍患者（n = 57）中，该模型对进展为AD的患者的敏感性为100%。混合建模方法完全独立于临床AD诊断，正确地对AD患者进行了分类。在超过三分之一的认知正常受试者中出现阿尔茨海默病的特征，这表明阿尔茨海默病的病理是活跃的，比以前预想的要早得多。
To identify biomarker patterns typical for Alzheimer disease (AD) in an independent, unsupervised way, without using information on the clinical diagnosis. Mixture modeling approach. Alzheimer’s Disease Neuroimaging Initiative database. Cognitively normal persons, patients with AD, and individuals with mild cognitive impairment. Cerebrospinal fluid–derived β-amyloid protein 1–42, total tau protein, and phosphorylated tau181P protein concentrations were used as biomarkers on a clinically well-characterized data set. The outcome of the qualification analysis was validated on 2 additional data sets, 1 of which was autopsy confirmed. Using the US Alzheimer’s Disease Neuroimaging Initiative data set, a cerebrospinal fluid β-amyloid protein 1–42/phosphorylated tau181P biomarker mixture model identified 1 feature linked to AD, while the other matched the “healthy” status. The AD signature was found in 90%, 72%, and 36% of patients in the AD, mild cognitive impairment, and cognitively normal groups, respectively. The cognitively normal group with the AD signature was enriched in apolipoprotein E ε4 allele carriers. Results were validated on 2 other data sets. In 1 study consisting of 68 autopsy-confirmed AD cases, 64 of 68 patients (94% sensitivity) were correctly classified with the AD feature. In another data set with patients (n = 57) with mild cognitive impairment followed up for 5 years, the model showed a sensitivity of 100% in patients progressing to AD. The mixture modeling approach, totally independent of clinical AD diagnosis, correctly classified patients with AD. The unexpected presence of the AD signature in more than one-third of cognitively normal subjects suggests that AD pathology is active and detectable earlier than has heretofore been envisioned.
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影响因子：
11
作者：
Gustafson, Deborah R.;Skoog, Ingmar;Blennow, Kaj
通讯作者：
Blennow, Kaj
DOI：
10.1073/pnas.0801227105
发表时间：
2008-06-10
影响因子：
11.1
作者：
Kauwe, John S. K.;Cruchaga, Carlos;Goate, Alison M.
通讯作者：
Goate, Alison M.
影响因子：
14.5
作者：
Pike, Kerryn E.;Savage, Greg;Rowe, Christopher C.
通讯作者：
Rowe, Christopher C.
影响因子：
2.4
作者：
Stomrud, Erik;Hansson, Oskar;Londos, Elisabet
通讯作者：
Londos, Elisabet
影响因子：
9.9
作者：
Bian, H.;Van Swieten, J. C.;Grossman, M.
通讯作者：
Grossman, M.