CSF biomarker variability in the Alzheimer's Association quality control program.
CSF biomarker variability in the Alzheimer's Association quality control program.
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DOI：
10.1016/j.jalz.2013.01.010
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Alzheimer's Association QC Program Work Group
中科院分区：
文献类型：
--
作者：
Mattsson N;Andreasson U;Persson S;Carrillo MC;Collins S;Chalbot S;Cutler N;Dufour-Rainfray D;Fagan AM;Heegaard NH;Robin Hsiung GY;Hyman B;Iqbal K;Kaeser SA;Lachno DR;Lleó A;Lewczuk P;Molinuevo JL;Parchi P;Regeniter A;Rissman RA;Rosenmann H;Sancesario G;Schröder J;Shaw LM;Teunissen CE;Trojanowski JQ;Vanderstichele H;Vandijck M;Verbeek MM;Zetterberg H;Blennow K;Alzheimer's Association QC Program Work Group
脑脊液（CSF）生物标志物淀粉样蛋白β 1-42、总tau蛋白和磷酸化tau蛋白越来越多地用于阿尔茨海默病（AD）研究和患者管理。然而，实验室之间和实验室内部的生物标志物测量存在很大差异。来自阿尔茨海默氏症协会质量控制程序的前九轮的数据用于定义分析变异性的程度和来源。在每轮中，通过单分析物酶联免疫吸附试验（ELISA）、多重xMAP试验或电化学发光检测免疫测定法分析在临床神经化学实验室（Mölndal，瑞典）制备的3份CSF样本。共有84个实验室参加。实验室间变异系数（CV）约为20%-30%;运行内CV小于5%-10%;实验室内纵向CV为5%-19%。有趣的是，纵向实验室内CV在各个实验室的生物标志物之间存在差异，这表明其组成部分具有检测依赖性。试剂盒批次之间和实验室之间的变异性对淀粉样蛋白β 1-42测量值都有重大影响，但对于总tau和磷酸化tau，试剂盒批次之间的影响远小于实验室之间的影响。尽管存在测量变异性，但样本分类的实验室间一致性（使用AD的predict-derived截止值）很高（ELISA的18份样本中有15份>90%，xMAP的18份样本中有12份> 90%）。总体变异性仍然过高，无法为特定预期用途分配通用生物标志物临界值。每个实验室必须确保其测量的纵向稳定性，并使用内部合格的截止水平。实验室程序的进一步标准化和试剂盒性能的改进可能会增加CSF AD生物标志物对研究人员和临床医生的有用性。
The cerebrospinal fluid (CSF) biomarkers amyloid beta 1–42, total tau, and phosphorylated tau are used increasingly for Alzheimer’s disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Data from the first nine rounds of the Alzheimer’s Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1–42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
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DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
12.7
作者：
Shaw LM;Vanderstichele H;Knapik-Czajka M;Figurski M;Coart E;Blennow K;Soares H;Simon AJ;Lewczuk P;Dean RA;Siemers E;Potter W;Lee VM;Trojanowski JQ;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
影响因子：
4
作者：
Mattsson, Niklas;Portelius, Erik;Zetterberg, Henrik
通讯作者：
Zetterberg, Henrik
DOI：
10.1016/j.jalz.2011.05.2243
发表时间：
2011-07
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Mattsson N;Andreasson U;Persson S;Arai H;Batish SD;Bernardini S;Bocchio-Chiavetto L;Blankenstein MA;Carrillo MC;Chalbot S;Coart E;Chiasserini D;Cutler N;Dahlfors G;Duller S;Fagan AM;Forlenza O;Frisoni GB;Galasko D;Galimberti D;Hampel H;Handberg A;Heneka MT;Herskovits AZ;Herukka SK;Holtzman DM;Humpel C;Hyman BT;Iqbal K;Jucker M;Kaeser SA;Kaiser E;Kapaki E;Kidd D;Klivenyi P;Knudsen CS;Kummer MP;Lui J;Lladó A;Lewczuk P;Li QX;Martins R;Masters C;McAuliffe J;Mercken M;Moghekar A;Molinuevo JL;Montine TJ;Nowatzke W;O'Brien R;Otto M;Paraskevas GP;Parnetti L;Petersen RC;Prvulovic D;de Reus HP;Rissman RA;Scarpini E;Stefani A;Soininen H;Schröder J;Shaw LM;Skinningsrud A;Skrogstad B;Spreer A;Talib L;Teunissen C;Trojanowski JQ;Tumani H;Umek RM;Van Broeck B;Vanderstichele H;Vecsei L;Verbeek MM;Windisch M;Zhang J;Zetterberg H;Blennow K
通讯作者：
Blennow K
DOI：
10.1007/bf02815140
发表时间：
1995-12-01
期刊：
MOLECULAR AND CHEMICAL NEUROPATHOLOGY
影响因子：
--
作者：
Blennow, K;Wallin, A;Vanmechelen, E
通讯作者：
Vanmechelen, E