Phosphorylated tau-Aβ42 ratio as a continuous trait for biomarker discovery for early-stage Alzheimer's disease in multiplex immunoassay panels of cerebrospinal fluid.
Phosphorylated tau-Aβ42 ratio as a continuous trait for biomarker discovery for early-stage Alzheimer's disease in multiplex immunoassay panels of cerebrospinal fluid.
复制标题
磷酸化的tau-Aβ42比是在脑脊液的多重免疫测定面板中发现生物标志物的连续特征。
DOI：
10.1016/j.biopsych.2013.11.032
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发表时间：
2014-05-01
影响因子：
10.6
通讯作者：
Goate, Alison M.
中科院分区：
文献类型：
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作者：
Harari, Oscar;Cruchaga, Carlos;Kauwe, John S. K.;Ainscough, Benjamin J.;Bales, Kelly;Pickering, Eve H.;Bertelsen, Sarah;Fagan, Anne M.;Holtzman, David M.;Morris, John C.;Goate, Alison M.
关键词：
识别阿尔茨海默病（AD）早期阶段发生的生理变化可能为疾病的诊断、预后和治疗提供重要见解。脑脊液（CSF）生物标志物是反映脑蛋白质组的丰富信息来源。我们应用了一种新的方法来筛选一组通过多重免疫测定定量的约190种CSF分析物，并检测Knight-Alzheimer病研究中心（ADRC;N=311）和阿尔茨海默病神经影像学倡议（ADNI;N=293）队列中的常见关联。在这些分析中，CSF ptau 181-Aβ42比值用作连续性状，而不是病例对照状态。我们证明ptau 181-Aβ42比值比传统建模方法具有更高的统计功效，并且CSF脂肪酸结合蛋白（H-FABP）和其他12种相关分析物的水平随着疾病进展而增加。使用传统的病例控制状态模型对这些结果进行了验证。对我们数据集的分层表明，这些分析物的增加发生在病程的非常早期，甚至在患有AD病理学的非痴呆个体中（低ptau 181，低Aβ42）与病理学阴性老年对照受试者（低ptau 181，高Aβ42）相比也很明显。FABP-Aβ42比率表明疾病转化为ptau 181-Aβ42的风险比相似，即使分类重叠不完全，表明FABP作为预测因子提供独立信息。我们的结果清楚地表明，本文提出的方法可用于正确鉴定AD的新生物标志物，并且CSF H-FABP水平在疾病的非常早期阶段开始增加。
Identification of the physiological changes that occur during the early stages of Alzheimer’s disease (AD) may provide critical insights for the diagnosis, prognosis and treatment of disease. Cerebrospinal fluid (CSF) biomarkers are a rich source of information that reflect the brain proteome. We applied a novel approach to screen a panel of ~190 CSF analytes quantified by multiplex immunoassay and detected common associations in the Knight- Alzheimer’s Disease Research Center (ADRC;N=311) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI;N=293) cohorts. CSF ptau181-Aβ42 ratio was used as a continuous trait, rather than case control status in these analyses. We demonstrate the ptau181-Aβ42 ratio has more statistical power than traditional modeling approaches and that the levels of CSF Fatty Acid Binding Protein (H-FABP) and 12 other correlated analytes increase as the disease progresses. These results were validated using the traditional case control status model. Stratification of our dataset demonstrated that increases in these analytes occur very early in the disease course and were apparent even in non-demented individuals with AD pathology (low ptau181, low Aβ42) compared to pathology-negative elderly control subjects (low ptau181, high Aβ42). FABP-Aβ42 ratio demonstrates a similar hazard ratio for disease conversion to ptau181-Aβ42 even though the overlap in classification is incomplete suggesting that FABP contributes independent information as a predictor Our results clearly indicate that the approach presented here can be employed to correctly identify novel biomarkers for AD, and that CSF H-FABP levels start to increase at very early stages of the disease.
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YKL-40：一种用于临床前阿尔茨海默病的新型预后液体生物标志物。
影响因子：
10.6
作者：
Craig-Schapiro, Rebecca;Perrin, Richard J.;Roe, Catherine M.;Xiong, Chengjie;Carter, Deborah;Cairns, Nigel J.;Mintun, Mark A.;Peskind, Elaine R.;Li, Ge;Galasko, Douglas R.;Clark, Christopher M.;Quinn, Joseph F.;D'Angelo, Gina;Malone, James P.;Townsend, R. Reid;Morris, John C.;Fagan, Anne M.;Holtzman, David M.
通讯作者：
Holtzman, David M.
影响因子：
12.7
作者：
Hu, William T.;Chen-Plotkin, Alice;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
2.1
作者：
Gao, Xiaoyi;Stamier, Joshua;Martin, Eden R.
通讯作者：
Martin, Eden R.
影响因子：
4.2
作者：
Price, Joseph L.;McKeel, Daniel W., Jr.;Buckles, Virginia D.;Roe, Catherine M.;Xiong, ChengJie;Grundman, Michael;Hansen, Lawrence A.;Petersen, Ronald C.;Parisi, Joseph E.;Dickson, Dennis W.;Smith, Charles D.;Davis, Daron G.;Schmitt, Frederick A.;Markesbery, William R.;Kaye, Jeffrey F.;Kurlan, Roger;Hulette, Christine;Kurland, Brenda F.;Higdon, Roger;Kukull, Walter;Morris, John C.
通讯作者：
Morris, John C.
影响因子：
30.8
作者：
通讯作者：
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