Assay of Plasma Phosphorylated Tau Protein (Threonine 181) and Total Tau Protein in Early-Stage Alzheimer's Disease
Assay of Plasma Phosphorylated Tau Protein (Threonine 181) and Total Tau Protein in Early-Stage Alzheimer's Disease
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DOI：
10.3233/jad-170810
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Yang, Shieh-Yueh
中科院分区：
文献类型：
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作者：
Yang, Che-Chuan;Chiu, Ming-Jang;Yang, Shieh-Yueh
探索了使用免疫磁性还原（IMR）测定血浆磷酸化tau蛋白（苏氨酸181）（表示为p-tau 181）的可行性。合成了IMR测定p-tau 181的试剂，并对其分析性能进行了表征。招募了73名受试者。每个参与者都接受了神经心理学测试，磁共振成像和血浆p-tau 181的IMR测定。使用市售IMR试剂盒，测定每个受试者的血浆总tau蛋白（T-tau）。使用IMR测定p-tau 181的动态范围为1.96 x 10（-2）pg/ml至10（4）pg/ml。在p-tau 181的测定中，总tau蛋白没有显著干扰。健康对照组血浆p-tau 181的测定浓度为2.46 +/- 1.09 pg/ml，AD所致MCI组为4.41 +/- 1.85 pg/ml，极轻度AD组为6.14 +/- 1.59 pg/ml。同时，健康对照的血浆T-tau的测量浓度为18.85 +/-10.16 pg/ml，AD导致的MCI为32.98 +/-10.18 pg/ml，极轻度AD为37.54 +/-12.29 pg/ml。在健康对照与AD所致MCI之间（p < 0.001）以及在AD所致MCI与极轻度AD之间（p <0.001）观察到血浆p-tau 181的显著差异。然而，对于血浆T-tau浓度，仅在健康对照和由AD引起的MCI之间存在显著差异（p < 0.001）。这意味着血浆p-tau 181水平与AD严重程度的相关性大于血浆T-tau。此外，在人血浆中观察到p-tau 181约占T-tau的14%。
The feasibility of assaying plasma phosphorylated tau protein (threonine 181), denoted p-tau181, using immuno-magnetic reduction (IMR) is explored. The reagent for assaying p-tau181 with IMR was synthesized, and its analytic performances were characterized. Seventy-three subjects were recruited. Each participant was examined with neuropsychological tests, magnetic resonance imaging, and IMR assay for plasma p-tau181. Using commercially available IMR kits, the plasma total tau protein (T-tau) of each subject was assayed. The dynamic range for assaying p-tau181 using IMR was 1.96 x 10(-2) pg/ml to 10(4) pg/ml. There was no significant interference from total tau protein in the assay of p-tau181. The measured concentrations of plasma p-tau181 were 2.46 +/- 1.09 pg/ml for healthy controls, 4.41 +/- 1.85 pg/ml for MCI due to AD, and 6.14 +/- 1.59 pg/ml for very mild AD. Meanwhile, the measured concentrations of plasma T-tau were 18.85 +/- 10.16 pg/ml for healthy controls, 32.98 +/- 10.18 pg/ml for MCI due to AD, and 37.54 +/- 12.29 pg/ml for very mild AD. A significant difference in plasma p-tau181 was observed between healthy controls and MCI due to AD (p < 0.001) and between MCI due to AD and very mild AD (p < 0.001). However, for the plasma T-tau concentration, a significant difference existed only between healthy controls and MCI due to AD (p < 0.001). This implies that the plasma p-tau181 level is correlated more to AD severity than plasma T-tau is. Additionally, p-tau181 was observed as approximately 14% of T-tau in human plasma.