Distribution of Aβ peptide in whole blood

The measurement of amyloid beta peptides (Aβ) in blood and plasma is expected to be a useful biomarker as potential therapeutics designed to lower Aβ peptide enter clinical trials. Many reports have suggested that Aβ could bind to substances in blood that may influence the recovery of Aβ peptide in plasma, its detection by conventional ELISAs or the actual turnover and half-life of the peptide in blood. In this study we describe a process for analyzing total Aβ in whole blood and plasma using denaturing solid-phase extraction followed by reverse-phase HPLC linked to ELISA. Comparison of total Aβ peptide levels in whole blood and plasma from the same bleed showed that most of the Aβ peptide is captured in the plasma if the samples are first denatured. In contrast, plasma that was assayed without denaturation could show greater than 70% reduction in apparent total Aβ peptide. This suggested that there was a pool of Aβ peptide in non-denatured plasma that is occluded from detection by ELISA, perhaps by binding to plasma proteins.