Determination of β-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry

Early pathogenic events in Alzheimer's disease (AD) involve increased production and/or reduced clearance of beta-amyloid (A beta), especially the 42 amino acid fragment A beta 1-42. The A beta 1-42 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 A beta peptides in cerebrospinal fluid (CSF). Using antibodies coupled to magnetic beads, we have detected 18 C-terminally and 2 N-terminally truncated A beta peptides in CSF. By determining the identity and profile of the truncated A beta peptides, more insight may be gained about differences in the metabolism and structural properties of A beta in AD. Finally, the A beta fragment signatures may prove useful as a diagnostic test for AD.