Ovod Vitaliy, Ramsey Kara N, Mawuenyega Kwasi G, Bollinger Jim G, Hicks Terry, Schneider Theresa, Sullivan Melissa, Paumier Katrina, Holtzman David M, Morris John C, Benzinger Tammie, Fagan Anne M, Patterson Bruce W, Bateman Randall J
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Alzheimers Dement. 2017 Aug;13(8):841-849. doi: 10.1016/j.jalz.2017.06.2266. Epub 2017 Jul 19.
Cerebrospinal fluid analysis and other measurements of amyloidosis, such as amyloid-binding positron emission tomography studies, are limited by cost and availability. There is a need for a more practical amyloid β (Aβ) biomarker for central nervous system amyloid deposition.
We adapted our previously reported stable isotope labeling kinetics protocol to analyze the turnover kinetics and concentrations of Aβ38, Aβ40, and Aβ42 in human plasma.
Aβ isoforms have a half-life of approximately 3 hours in plasma. Aβ38 demonstrated faster turnover kinetics compared with 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 cerebrospinal fluid, suggesting a blood-brain transportation mechanism of Aβ. The stability and sensitivity of plasma Aβ measurements suggest this may be a useful screening test for central nervous system amyloidosis.
脑脊液分析以及其他淀粉样变性检测方法，如淀粉样蛋白结合正电子发射断层扫描研究，受到成本和可及性的限制。因此需要一种更实用的用于中枢神经系统淀粉样蛋白沉积的淀粉样β（Aβ）生物标志物。
我们采用先前报道的稳定同位素标记动力学方案，分析人血浆中Aβ38、Aβ40和Aβ42的周转动力学及浓度。
Aβ亚型在血浆中的半衰期约为3小时。与Aβ40和Aβ42相比，Aβ38表现出更快的周转动力学。在淀粉样蛋白阳性参与者中，观察到Aβ42相对于Aβ40的更快的分数周转率以及更低的Aβ42和Aβ42/Aβ40浓度。
血浆Aβ42显示出与我们先前在脑脊液中报道的类似的淀粉样蛋白相关改变，提示Aβ存在血脑转运机制。血浆Aβ检测的稳定性和敏感性表明，这可能是一种用于中枢神经系统淀粉样变性的有用筛查试验。
