Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis.

Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis.
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淀粉样蛋白β浓度和稳定的同位素标记人血浆特异性淀粉样变性的动力学。

DOI:
10.1016/j.jalz.2017.06.2266
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发表时间:
2017-08
期刊:
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子:
--
通讯作者:
Bateman RJ
Bateman RJ
中科院分区:
其他
文献类型:
--
作者:
Ovod V;Ramsey KN;Mawuenyega KG;Bollinger JG;Hicks T;Schneider T;Sullivan M;Paumier K;Holtzman DM;Morris JC;Benzinger T;Fagan AM;Patterson BW;Bateman RJ

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CSF分析和淀粉样变性的其他测量,如淀粉样蛋白结合正电子发射断层扫描(PET)研究,受到成本和可用性的限制。中枢神经系统(CNS)淀粉样蛋白沉积需要更实用的Aβ生物标志物。我们调整了先前报告的稳定同位素标记动力学(SILK)方案,以分析人血浆中Aβ38、Aβ40和Aβ42的转换动力学和浓度。Aβ亚型在血浆中的半衰期约为3小时。与Aβ40和Aβ42相比,Aβ38表现出更快的转换动力学。在淀粉样蛋白阳性受试者中,观察到Aβ42相对于Aβ40的更新分数更快,Aβ42和Aβ42/Aβ40浓度更低。血浆Aβ42显示出与我们先前在CSF中报道的类似的淀粉样蛋白相关改变,表明Aβ的血脑转运机制。血浆Aβ测定的稳定性和敏感性表明,这可能是一个有用的中枢神经系统淀粉样变性的筛查试验。
CSF analysis and other measurements of amyloidosis, such as amyloid-binding positron emission tomography (PET) studies, are limited by cost and availability. There is a need for a more practical Aβ biomarker for central nervous system (CNS) amyloid deposition. We adapted our previously reported Stable Isotope Labeling Kinetics (SILK) protocol to analyze the turnover kinetics and concentrations of Aβ38, Aβ40, and Aβ42 in human plasma. Aβ isoforms have a half-life of approximately three hours in plasma. Aβ38 demonstrated faster turnover kinetics compared to Aβ40 and Aβ42. Faster fractional turnover of Aβ42 relative to Aβ40 and lower Aβ42 and Aβ42/Aβ40 concentrations in amyloid positive participants were observed. Blood plasma Aβ42 shows similar amyloid-associated alterations as we have previously reported in CSF, suggesting a blood-brain transportation mechanism of Aβ. The stability and sensitivity of plasma Aβ measurements suggests this may be a useful screening test for CNS amyloidosis.
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