Identification and quantification of amyloid beta-related peptides in human plasma using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Proteolytic processing of the amyloid precursor protein (APP) by beta-secretase and gamma-secretase leads to the generation and deposition of amyloid beta (A beta) in Alzheimer's disease (AD). N-terminally or C-terminally truncated A beta variants have been found in human cerebrospinal fluid and cultured cell media using immunoprecipitation and mass spectrometry. Unfortunately, the profile of plasma A beta variants has not been revealed due to the difficulty of isolating A beta from plasma. We present here for the first time studies of A beta and related peptides in human plasma. Twenty-two A beta-related peptides including novel peptides truncated before the beta-secretase site were detected in human plasma and 20 of the peptides were identified by tandem mass spectrometry. Using an internal standard, we developed a quantitative assay for the A beta-related peptides and demonstrated plasma dilution linearity and the precision required for their quantitation. The present method should enhance the understanding of APP processing and clearance in AD progression.