Laser-Induced In-Source Decay Applied to the Determination of Amyloid-Beta in Alzheimer’s Brains

• Published in: ACS chemical neuroscience Vol. 7; no. 3; pp. 261 - 268
• Main Authors: Kelley, Andrea R, Perry, George, Castellani, Rudolph J, Bach, Stephan B. H
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.03.2016
• Subjects: Alzheimer Disease - diagnostic imaging; Alzheimer Disease - pathology; Amyloid beta-Peptides - analysis; Female; Humans; Male; Plaque, Amyloid - diagnostic imaging; Plaque, Amyloid - pathology; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Tandem Mass Spectrometry; amyloid-beta; mass spectrometry; Alzheimer’s disease; imaging; MALDI
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.5b00295

A method for the analysis of amyloid-beta peptides in isolated plaques and intact tissue sections affected by Alzheimer’s disease (AD) is presented. This method employs matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry and the inherent laser-induced in-source decay (ISD) that occurs coupled with imaging mass spectrometry (IMS) to investigate the composition of these samples eliminating the need for other confirmational MS/MS techniques. These results demonstrate this technique’s usefulness for the identification of amyloid-beta peptides in tissue and isolated senile plaques from AD patients using the reproducible fragmentation pattern demonstrated via the laser-induced ISD of synthetic amyloid-beta peptide clips (1–40, 1–42). Clear differences between the hippocampal AD tissue and the control hippocampal tissue regarding the presence of amyloid-beta have been identified. These are based on laser-induced ISD of standard amyloid-beta clips as controls as well as the analysis of isolated senile plaques as a confirmation before tissue analysis. Using the resulting observed peptide clip masses from the control data, we present mass spectrometry based identification of the amyloid-beta peptides in both isolated plaques and hippocampal regions of those patients diagnosed with AD.