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

Introduction: 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 beta (A beta) biomarker for central nervous system amyloid deposition. Methods: We adapted our previously reported stable isotope labeling kinetics protocol to analyze the turnover kinetics and concentrations of A beta 38, A beta 40, and A beta 42 in human plasma. Results: A beta isoforms have a half-life of approximately 3 hours in plasma. A beta 38 demonstrated faster turnover kinetics compared with A beta 40 and A beta 42. Faster fractional turnover of A beta 42 relative to A beta 40 and lower A beta 42 and A beta 42/A beta 40 concentrations in amyloid-positive participants were observed. Discussion: Blood plasma A beta 42 shows similar amyloid-associated alterations as we have previously reported in cerebrospinal fluid, suggesting a blood-brain transportation mechanism of A beta. The stability and sensitivity of plasma A beta measurements suggest this may be a useful screening test for central nervous system amyloidosis. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.