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

中枢神经系统淀粉样变性人血浆中淀粉样蛋白β浓度和稳定同位素标记动力学

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作者:Vitaliy Ovod, Kara N Ramsey, Kwasi G Mawuenyega, Jim G Bollinger, Terry Hicks, Theresa Schneider, Melissa Sullivan, Katrina Paumier, David M Holtzman, John C Morris, Tammie Benzinger, Anne M Fagan, Bruce W Patterson, Randall J Bateman

Discussion

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.

Methods

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.

Results

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.

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