Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects.
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects.
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DOI：
10.1002/ana.21610
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发表时间：
2009-04
影响因子：
11.2
通讯作者：
Trojanowski, John Q.
中科院分区：
文献类型：
--
作者：
Shaw, Leslie M.;Vanderstichele, Hugo;Knapik-Czajka, Malgorzata;Clark, Christopher M.;Aisen, Paul S.;Petersen, Ronald C.;Blennow, Kaj;Soares, Holly;Simon, Adam;Lewczuk, Piotr;Dean, Robert;Siemers, Eric;Potter, William;Lee, Virginia M. -Y.;Trojanowski, John Q.
在阿尔茨海默病神经影像学倡议（ADNI）受试者中开发轻度阿尔茨海默病（AD）的脑脊液生物标志物签名。(1)对100例轻度AD、196例轻度认知障碍和114例老年ADNI认知正常（NC）受试者进行基线评估时获得的脑脊液（CSF）样本进行了淀粉样蛋白-β 1-42肽（Aβ1-42）、总tau （t-tau）和苏氨酸181磷酸化的tau的测量；(2) 56例尸检证实的AD病例和52例年龄匹配的老年nc，采用多重免疫分析。利用尸检证实的脑脊液数据得出的接受者工作特征切点和逻辑回归模型，检测ADNI受试者的AD脑脊液中t-tau和Aβ1-42的谱。脑脊液Aβ1-42是脑脊液样本尸检队列中最敏感的AD生物标志物：受试者工作特征曲线下面积为0.913，AD检测灵敏度为96.4%。在ADNI队列中，a β1-42、t-tau和APOε4等位基因计数的logistic回归模型提供了轻度AD的最佳评估描述。在37名ADNI轻度认知障碍受试者中，有33名在研究的第一年转化为可能的AD，检测到t-tau/ a - β1-42的AD样基线CSF谱。在一项大型、多地点、前瞻性临床研究中，a β1-42和t-tau定义的AD脑脊液生物标志物特征在尸检证实的AD队列中以及在ADNI随访12个月的队列中被证实，可以检测到轻度AD，并且这种特征似乎可以预测从轻度认知障碍到AD的转化。
Develop a cerebrospinal fluid biomarker signature for mild Alzheimer’s disease (AD) in Alzheimer’s Disease Neuroimaging Initiative (ADNI) subjects. Amyloid-β 1 to 42 peptide (Aβ1-42), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and Aβ1-42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data. CSF Aβ1-42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1-42, t-tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/Aβ1-42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. The CSF biomarker signature of AD defined by Aβ1-42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD.
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影响因子：
3.5
作者：
Zhang, Jing;Sokal, Izabela;Montine, Thomas J.
通讯作者：
Montine, Thomas J.
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：
9.3
作者：
Reijn, Thierry S. M.;Rikkert, Marcel Olde;Verbeek, Marcel M.
通讯作者：
Verbeek, Marcel M.
影响因子：
9.9
作者：
Li, G.;Sokal, I.;Montine, T. J.
通讯作者：
Montine, T. J.