Amyloid-β peptides interact with plasma proteins and erythrocytes: Implications for their quantitation in plasma

Yu Min Kuo, Tyler A. Kokjohn, Walter Kalback, Dean Luehrs, Douglas R. Galasko, Nathalie Chevallier, Edward H. Koo, Mark R. Emmerling, Alex E. Roher

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162 Citations (Scopus)

Abstract

Amyloid β peptides are bound rapidly in the plasma complicating an accurate assessment of their in vivo abundance by immunoassay procedures. The extent of Aβ immunoassay interference was used to estimate the Aβ binding capacity of purified plasma proteins, erythrocytes and whole plasma. Human serum albumin bound Aβ peptides rapidly with a 1:1 stoichiometry and at physiological concentrations was capable of binding over 95% of an input of 5 ng/ml Aβ. Purified α2-macroglobulin was able to bind Aβ peptides and at physiological concentration bound 73% of 5 ng/ml of Aβ. Erythrocytes also sequestered the Aβ peptides, showing a preference for binding Aβ 1-42. Incubation of 5 ng/ml of Aβ in plasma revealed that about 30% of the peptides were still detectable by immunoassay, presumably reflecting the binding of Aβ peptides with albumin and other plasma molecules. Thus, our studies reveal that both the soluble and formed elements of the blood are capable of sequestering Aβ peptides. To avoid underestimating plasma Aβ values, we employed an improved column chromatography method under denaturing conditions to liberate Aβ from its associations with plasma proteins. Quantification of Aβ 40 and 42 levels in plasma from both normal and AD individuals after chromatography showed a large overlap between AD and control groups, despite the very large pool of Aβ present in the AD brains. The potential origins of the plasma Aβ pool are discussed. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)750-756
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume268
Issue number3
DOIs
Publication statusPublished - 2000 Feb 24

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kuo, Y. M., Kokjohn, T. A., Kalback, W., Luehrs, D., Galasko, D. R., Chevallier, N., Koo, E. H., Emmerling, M. R., & Roher, A. E. (2000). Amyloid-β peptides interact with plasma proteins and erythrocytes: Implications for their quantitation in plasma. Biochemical and Biophysical Research Communications, 268(3), 750-756. https://doi.org/10.1006/bbrc.2000.2222