title: Laser-Induced In-Source Decay Applied to the Determination of Amyloid-Beta in Alzheimer's Brains.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Texas at San Antonio , One UTSA Circle, San Antonio, Texas 78249, United States.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Kelley
authors.affiliation: College of Sciences, University of Texas at San Antonio , One UTSA Circle, San Antonio, Texas 78249, United States.
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.affiliation: Department of Pathology, School of Medicine, University of Maryland , 22 South Greene St., Baltimore, Maryland 21201, United States.
authors.forename: Rudolph J
authors.initials: RJ
authors.lastname: Castellani
authors.affiliation: Department of Chemistry, University of Texas at San Antonio , One UTSA Circle, San Antonio, Texas 78249, United States.
authors.forename: Stephan B H
authors.initials: SB
authors.lastname: Bach
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer’s disease; MALDI; amyloid-beta; imaging; mass spectrometry