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

Alzheimers Dement. 2017 Aug;13(8):841-849. doi: 10.1016/j.jalz.2017.06.2266. Epub 2017 Jul 19.

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.

Keywords: Amyloid β; Aβ42; Human; Kinetics; Plasma; Turnover.

MeSH terms

  • Aged
  • Amyloid beta-Peptides / blood*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloidosis / blood*
  • Amyloidosis / cerebrospinal fluid
  • Amyloidosis / diagnostic imaging
  • Area Under Curve
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Chromatography, Liquid
  • Humans
  • Immunoprecipitation
  • Isotope Labeling
  • Kinetics
  • Mass Spectrometry
  • Peptide Fragments / blood*
  • Peptide Fragments / cerebrospinal fluid
  • Prospective Studies
  • ROC Curve
  • Single-Blind Method

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-38)
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)