Modification of amyloid-beta(1-40) by a protease inhibitor creates risk of error in mass spectrometric quantitation of amyloid-beta(1-42).

Matrix-assisted laser desorption mass spectrometry successfully analyzes mixed populations of amyloid-beta (Abeta) peptides, providing a profile in which changes caused by drug action are directly observed. A spectrum of Abeta immunocaptured from guinea pig brain included a novel component with monoisotopic [M+H]+ at 4511.22, close to the monoisotopic value of [M+H]+ for Abeta(1-42) of 4512.27 and overlapping and interfering with the authentic Abeta(1-42) peak. Hypothesis and experiment led to the conclusion that modification of Abeta(1-40) by the protease inhibitor aminoethylbenzenesulfonyl fluoride generates a product with monoisotopic [M+H]+ at 4511.19, and that this accounts for the interfering peak.