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使用2种分析平台比较阿尔茨海默病和额颞叶变性患者脑脊液中tau蛋白和Aβ 1-42水平。

Comparison of cerebrospinal fluid levels of tau and Aβ 1-42 in Alzheimer disease and frontotemporal degeneration using 2 analytical platforms.

作者信息

Irwin David J, McMillan Corey T, Toledo Jon B, Arnold Steven E, Shaw Leslie M, Wang Li-San, Van Deerlin Vivianna, Lee Virginia M-Y, Trojanowski John Q, Grossman Murray

机构信息

Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.

出版信息

Arch Neurol. 2012 Aug;69(8):1018-25. doi: 10.1001/archneurol.2012.26.

Abstract

OBJECTIVE

To use values of cerebrospinal fluid tau and β-amyloid obtained from 2 different analytical immunoassays to differentiate Alzheimer disease (AD) from frontotemporal lobar degeneration (FTLD).

DESIGN

Cerebrospinal fluid values of total tau (T-tau) and β-amyloid 1-42 (Aβ 1-42) obtained using the Innotest enzyme-linked immunosorbent assay were transformed using a linear regression model to equivalent values obtained using the INNO-BIA AlzBio3 (xMAP; Luminex) assay. Cutoff values obtained from the xMAP assay were developed in a series of autopsy-confirmed cases and cross validated in another series of autopsy-confirmed samples using transformed enzyme-linked immunosorbent assay values to assess sensitivity and specificity for differentiating AD from FTLD.

SETTING

Tertiary memory disorder clinics and neuropathologic and biomarker core centers.

PARTICIPANTS

Seventy-five samples from patients with cerebrospinal fluid data obtained from both assays were used for transformation of enzyme-linked immunosorbent assay values. Forty autopsy-confirmed cases (30 with AD and 10 with FTLD) were used to establish diagnostic cutoff values and then cross validated in a second sample set of 21 autopsy-confirmed cases (11 with AD and 10 with FTLD) with transformed enzyme-linked immunosorbent assay values.

MAIN OUTCOME MEASURE

Diagnostic accuracy using transformed biomarker values.

RESULTS

Data obtained from both assays were highly correlated. The T-tau to Aβ 1-42 ratio had the highest correlation between measures (r = 0.928, P < .001) and high reliability of transformation (intraclass correlation coefficient= 0.89). A cutoff of 0.34 for the T-tau to Aβ 1-42 ratio had 90% and 100% sensitivity and 96.7% and 91% specificity to differentiate FTLD cases in the validation and cross-validation samples, respectively.

CONCLUSIONS

Values from 2 analytical platforms can be transformed into equivalent units, which can distinguish AD from FTLD more accurately than the clinical diagnosis.

摘要

目的

利用从两种不同分析免疫测定法获得的脑脊液tau蛋白和β-淀粉样蛋白值,区分阿尔茨海默病(AD)和额颞叶变性(FTLD)。

设计

使用Innotest酶联免疫吸附测定法获得的总tau蛋白(T-tau)和β-淀粉样蛋白1-42(Aβ 1-42)的脑脊液值,通过线性回归模型转换为使用INNO-BIA AlzBio3(xMAP;Luminex)测定法获得的等效值。在一系列尸检确诊病例中确定xMAP测定法的临界值,并使用转换后的酶联免疫吸附测定值在另一系列尸检确诊样本中进行交叉验证,以评估区分AD和FTLD的敏感性和特异性。

地点

三级记忆障碍诊所以及神经病理学和生物标志物核心中心。

参与者

来自75名患者的样本,这些患者的脑脊液数据通过两种测定法获得,用于酶联免疫吸附测定值的转换。40例尸检确诊病例(30例AD和10例FTLD)用于确定诊断临界值,然后在第二组21例尸检确诊病例(11例AD和10例FTLD)中使用转换后的酶联免疫吸附测定值进行交叉验证。

主要观察指标

使用转换后的生物标志物值的诊断准确性。

结果

两种测定法获得的数据高度相关。T-tau与Aβ 1-42比值在各项指标之间具有最高的相关性(r = 0.928,P <.001),且转换具有高可靠性(组内相关系数 = 0.89)。T-tau与Aβ 1-42比值的临界值为0.34时,在验证样本和交叉验证样本中分别有90%和100%的敏感性以及96.7%和91%的特异性来区分FTLD病例。

结论

来自两个分析平台的值可以转换为等效单位,与临床诊断相比,其能够更准确地区分AD和FTLD。

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