Improved protocol for measurement of plasma β-amyloid in longitudinal evaluation of Alzheimer's Disease Neuroimaging Initiative study patients.
Improved protocol for measurement of plasma β-amyloid in longitudinal evaluation of Alzheimer's Disease Neuroimaging Initiative study patients.
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DOI：
10.1016/j.jalz.2012.01.001
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Figurski MJ;Waligórska T;Toledo J;Vanderstichele H;Korecka M;Lee VM;Trojanowski JQ;Shaw LM;Alzheimer’s Disease Neuroimaging Initiative
各中心血浆β-淀粉样蛋白（a β）测量的测定间变异性和不一致性是排除结果解释的主要因素，也是该生物标志物研究间荟萃分析的重大障碍。本研究的目的是通过提高生物分析方法的性能来解决这些问题。我们使用了Luminex免疫分析平台和Innogenetics的基于多路微球的试剂盒。机器人移液系统用于执行程序的关键步骤。使用来自志愿者的两个试剂盒对照样本和两个质量对照血浆样本对该方法的性能进行评估，并在每次运行中重新测试先前检测的患者样本。该装置用于处理来自阿尔茨海默病神经成像倡议研究生物液库的2454例患者血浆样本。我们还使用混合效应模型评估了我们的结果与脑脊液（CSF）生物标志物数据之间的相关性。试剂盒对照Aβ1-40和Aβ1-42的平均精密度分别为8.3%和4.0%，血浆质量对照Aβ1-40和Aβ1-42的平均精密度分别为6.4%和4.8%。复测结果表明，Aβ1-40的平均精密度为7.2%，Aβ1-42的平均精密度为4.5%。阿尔茨海默病神经成像倡议患者的最终血浆结果范围为Aβ1-40为13至372 pg/mL（中位数：164 pg/mL）， Aβ1-42为3.5至103 pg/mL（中位数：39.3 pg/mL）。我们发现样本采集参数（血容量和冻结时间）对结果的影响很小，但很重要。阿尔茨海默病患者与健康对照者血浆Aβ水平无显著差异。我们已经确定了血浆Aβ1-42水平与脑脊液生物标志物的多重显著相关性。在轻度认知障碍患者中，血浆a - β1-42水平与CSF p-tau181/ a - β1-42比值之间存在相对最强的相关性。当我们使用纵向数据时，血浆Aβ1-40与脑脊液生物标志物的相关性较弱且完全减弱。血浆Aβ1-42/Aβ1-40比值无显著相关性。我们的机器人化方法的精度比文献中报道的结果有了实质性的改进。血浆和脑脊液生物标志物之间存在多种显著相关性。虽然这些相关性不足以支持血浆a β测量作为诊断筛选试验，但血浆a β1-42水平非常适合用作药效学标志物。
The interassay variability and inconsistency of plasma β-amyloid (Aβ) measurements among centers are major factors precluding the interpretation of results and a substantial obstacle in the meta-analysis across studies of this biomarker. The goal of this investigation was to address these problems by improving the performance of the bioanalytical method. We used the Luminex immunoassay platform with a multiplex microsphere-based reagent kit from Innogenetics. A robotic pipetting system was used to perform crucial steps of the procedure. The performance of this method was evaluated using two kit control samples and two quality control plasma samples from volunteer donors, and by retesting previously assayed patient samples in each run. This setup was applied to process 2454 patient plasma samples from the Alzheimer's Disease Neuroimaging Initiative study biofluid repository. We have additionally evaluated the correlations between our results and cerebrospinal fluid (CSF) biomarker data using mixed-effects modeling. The average precision values of the kit controls were 8.3% for Aβ1-40 and 4.0% for Aβ1-42, whereas the values for the plasma quality controls were 6.4% for Aβ1-40 and 4.8% for Aβ1-42. From the test–retest evaluation, the average precision was 7.2% for Aβ1-40 and 4.5% for Aβ1-42. The range of final plasma results for Alzheimer's Disease Neuroimaging Initiative patients was 13 to 372 pg/mL (median: 164 pg/mL) for Aβ1-40 and 3.5 to 103 pg/mL (median: 39.3 pg/mL) for Aβ1-42. We found that sample collection parameters (blood volume and time to freeze) have a small, but significant, influence on the result. No significant difference was found between plasma Aβ levels for patients with Alzheimer's disease and healthy control subjects. We have determined multiple significant correlations of plasma Aβ1-42 levels with CSF biomarkers. The relatively strongest, although modest, correlation was found between plasma Aβ1-42 levels and CSF p-tau181/Aβ1-42 ratio in patients with mild cognitive impairment. Plasma Aβ1-40 correlations with CSF biomarkers were weaker and diminished completely when we used longitudinal data. No significant correlations were found for the plasma Aβ1-42/Aβ1-40 ratio. The precision of our robotized method represents a substantial improvement over results reported in the literature. Multiple significant correlations between plasma and CSF biomarkers were found. Although these correlations are not strong enough to support the use of plasma Aβ measurement as a diagnostic screening test, plasma Aβ1-42 levels are well suited for use as a pharmacodynamic marker.
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DOI：
10.1136/jnnp.2010.205757
发表时间：
2010-10
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Seppälä TT;Herukka SK;Hänninen T;Tervo S;Hallikainen M;Soininen H;Pirttilä T
通讯作者：
Pirttilä T
影响因子：
9.9
作者：
Ringman, J. M.;Younkin, S. G.;Cummings, J. L.
通讯作者：
Cummings, J. L.
影响因子：
7.2
作者：
Blasko, Imrich;Kemmler, Georg;Fischer, Peter
通讯作者：
Fischer, Peter
影响因子：
12.7
作者：
Toledo JB;Vanderstichele H;Figurski M;Aisen PS;Petersen RC;Weiner MW;Jack CR Jr;Jagust W;Decarli C;Toga AW;Toledo E;Xie SX;Lee VM;Trojanowski JQ;Shaw LM;Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
影响因子：
4.4
作者：
Ma Fei;Wang Jianghua;Wang Qian
通讯作者：
Wang Qian