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O3–01–04: Determination of beta–amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation–mass spectrometry
Author(s) -
Portelius Erik,
Westman-Brinkmalm Ann,
Zetterberg Henrik,
Blennow Kaj
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.190
Subject(s) - peptide , chemistry , immunoprecipitation , epitope , antibody , cerebrospinal fluid , molecular mass , mass spectrometry , neprilysin , amyloid beta , biochemistry , microbiology and biotechnology , enzyme , chromatography , biology , immunology , gene , neuroscience
Early pathogenic events in Alzheimer's disease (AD) involve increased production and/or reduced clearance of beta-amyloid (Abeta), especially the 42 amino acid fragment Abeta1-42. The Abeta1-42 peptide is generated through cleavage of the amyloid precursor protein by beta- and gamma-secretase and is catabolised by a variety of proteolytic enzymes such as insulin-degrading enzyme and neprilysin. Here, we describe a method that employs immunoprecipitation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to determine the pattern of C-terminally truncated Abeta peptides in cerebrospinal fluid (CSF). Using antibodies coupled to magnetic beads, we have detected 18 C-terminally and 2 N-terminally truncated Abeta peptides in CSF. By determining the identity and profile of the truncated Abeta peptides, more insight may be gained about differences in the metabolism and structural properties of Abeta in AD. Finally, the Abeta fragment signatures may prove useful as a diagnostic test for AD.