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

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• 作者：Andrea R. Kelley ; George Perry ; Rudolph J. Castellani ; Stephan B. H. Bach
• 刊名：ACS Chemical Neuroscience
• 出版年：2016
• 出版时间：March 16, 2016
• 年：2016
• 卷：7
• 期：3
• 页码：261-268
• 全文大小：351K
• ISSN：1948-7193

文摘

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.