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ACS Chem Neurosci. 2016 Mar 16;7(3):261-8. doi: 10.1021/acschemneuro.5b00295. Epub 2016 Jan 6.

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

Author information

1
Department of Chemistry, University of Texas at San Antonio , One UTSA Circle, San Antonio, Texas 78249, United States.
2
College of Sciences, University of Texas at San Antonio , One UTSA Circle, San Antonio, Texas 78249, United States.
3
Department of Pathology, School of Medicine, University of Maryland , 22 South Greene St., Baltimore, Maryland 21201, United States.

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.

KEYWORDS:

Alzheimer’s disease; MALDI; amyloid-beta; imaging; mass spectrometry

PMID:
26720297
DOI:
10.1021/acschemneuro.5b00295
[Indexed for MEDLINE]

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