Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
Original Articles
Identification and quantification of amyloid beta-related peptides in human plasma using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
Naoki KANEKORie YAMAMOTOTaka-Aki SATOKoichi TANAKA
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2014 年 90 巻 3 号 p. 104-117

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Proteolytic processing of the amyloid precursor protein (APP) by β-secretase and γ-secretase leads to the generation and deposition of amyloid β (Aβ) in Alzheimer’s disease (AD). N-terminally or C-terminally truncated Aβ variants have been found in human cerebrospinal fluid and cultured cell media using immunoprecipitation and mass spectrometry. Unfortunately, the profile of plasma Aβ variants has not been revealed due to the difficulty of isolating Aβ from plasma. We present here for the first time studies of Aβ and related peptides in human plasma. Twenty-two Aβ-related peptides including novel peptides truncated before the β-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 Aβ-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.

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© 2014 The Japan Academy
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