Distribution of Abeta peptide in whole blood.
The measurement of amyloid beta peptides (Abeta) in blood and plasma is expected to be a useful biomarker as potential therapeutics designed to lower Abeta peptide enter clinical trials. Many reports have suggested that Abeta could bind to substances in blood that may influence the recovery of Abeta 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 Abeta in whole blood and plasma using denaturing solid-phase extraction followed by reverse-phase HPLC linked to ELISA. Comparison of total Abeta peptide levels in whole blood and plasma from the same bleed showed that most of the Abeta 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 Abeta peptide. This suggested that there was a pool of Abeta peptide in non-denatured plasma that is occluded from detection by ELISA, perhaps by binding to plasma proteins.
Slemmon
J Randall
JR
Genomics and Biotechnology, Pfizer Global Research and Development, Skokie, IL 60077, USA. Randy.Slemmon@bms.com
Painter
Cory L
CL
Nadanaciva
Sashi
S
Catana
Florentina
F
Cook
Ashley
A
Motter
Ruth
R
Seubert
Peter
P
D000328:Adult; D016229:Amyloid beta-Peptides / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D016229:Amyloid beta-Peptides