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早期痴呆症和轻度认知障碍患者脑脊液中痴呆生物标志物的多重定量:一项多中心研究。

Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: a multicenter study.

作者信息

Lewczuk Piotr, Kornhuber Johannes, Vanderstichele Hugo, Vanmechelen Eugeen, Esselmann Hermann, Bibl Mirko, Wolf Stefanie, Otto Markus, Reulbach Udo, Kölsch Heike, Jessen Frank, Schröder Johannes, Schönknecht Peter, Hampel Harald, Peters Oliver, Weimer Erik, Perneczky Robert, Jahn Holger, Luckhaus Christian, Lamla Ulrich, Supprian Tillmann, Maler Juan Manuel, Wiltfang Jens

机构信息

Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany.

出版信息

Neurobiol Aging. 2008 Jun;29(6):812-8. doi: 10.1016/j.neurobiolaging.2006.12.010. Epub 2007 Jan 19.

Abstract

In this report we evaluated the clinical performance of APOE genotyping and three protein biomarkers (total tau, beta-amyloid(1-42), and tau phosphorylated at threonine 181) in a prospective multicenter study using the INNO-BIA AlzBio3 assay applied on Luminex platform. Concentration of biomarkers of Alzheimer's disease in cerebrospinal fluid (CSF) was measured with multiplexing technology (n=223), and compared to the results of ELISA assays in patients with early dementias or mild cognitive impairment (MCI) collected at 12 gerontopsychiatric university departments, and APOE genotyping was performed. Concentrations of Abeta(1-42) were statistically significantly lower in MCI-AD subjects compared to MCI-O, and significantly lower in D-AD patients compared to MCI-O. P-tau(181P) concentrations were significantly higher in MCI-AD patients compared to MCI-O, and significantly higher in D-AD patients compared to MCI-O. The total tau concentrations in MCI-AD patients were significantly higher compared to MCI-O, and higher in D-AD compared to MCI-O, moreover, the concentration of total tau was significantly higher in D-AD compared to MCI-AD patients. For the differential diagnosis between D-AD and D-O, the optimal cutoff concentration of Abeta(1-42) was 197.7 pg/mL, and that for P-tau(181P) was 47.9 pg/mL. These cutoff values were also applied to discriminate between MCI-AD and MCI-O subjects. Simultaneous measurement of the biomarkers significantly improves management of the samples and quality control of the assays' performance.

摘要

在本报告中,我们在一项前瞻性多中心研究中评估了载脂蛋白E(APOE)基因分型及三种蛋白质生物标志物(总tau蛋白、β淀粉样蛋白(1-42)和苏氨酸181位点磷酸化的tau蛋白)的临床性能,该研究使用了应用于Luminex平台的INNO-BIA AlzBio3检测法。采用多重技术测定了223例脑脊液(CSF)中阿尔茨海默病生物标志物的浓度,并将其与在12个老年精神科大学科室收集的早期痴呆或轻度认知障碍(MCI)患者的酶联免疫吸附测定(ELISA)结果进行比较,同时进行了APOE基因分型。与MCI-O组相比,MCI-AD组受试者的β淀粉样蛋白(1-42)浓度在统计学上显著降低,与MCI-O组相比,痴呆型阿尔茨海默病(D-AD)患者的该浓度也显著降低。与MCI-O组相比,MCI-AD患者的磷酸化tau蛋白(181P)浓度显著升高,与MCI-O组相比,D-AD患者的该浓度也显著升高。与MCI-O组相比,MCI-AD患者的总tau蛋白浓度显著升高,与MCI-O组相比,D-AD患者的该浓度更高,此外,与MCI-AD患者相比,D-AD患者的总tau蛋白浓度显著更高。对于D-AD与非痴呆(D-O)的鉴别诊断,β淀粉样蛋白(1-42)的最佳临界浓度为197.7 pg/mL,磷酸化tau蛋白(181P)的最佳临界浓度为47.9 pg/mL。这些临界值也用于区分MCI-AD和MCI-O受试者。同时检测这些生物标志物可显著改善样本管理和检测性能的质量控制。

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