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

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

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

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 β (Aβ) 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 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. 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.

Original languageEnglish
Pages (from-to)841-849
Number of pages9
JournalAlzheimer's and Dementia
Volume13
Issue number8
DOIs
StatePublished - Aug 2017

Keywords

  • Amyloid β
  • Aβ42
  • Human
  • Kinetics
  • Plasma
  • Turnover

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