Molecular Mapping Alzheimer's Disease: MALDI Imaging of Formalin-fixed, Paraffin-embedded Human Hippocampal Tissue



Andrea R. Kelley1, George Perry1, *, Chloe Bethea1, Rudolph J. Castellani2, Stephan B.H. Bach1
1 College of Sciences, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX. 78249, USA
2 Department of Pathology, School of Medicine, University of Maryland, 22 South Greene St. Baltimore, MD. 21201, USA


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© Kelley et al.; Licensee Bentham Open

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at The University of Texas at San Antonio, One UTSA Circle, Bioscience Engineering Bulding Rm.2.110, San Antonio, TX. 78249, USA; Tel: 210-458-4450; Fax: 210-458-4445; E-mail: george.perry@utsa.edu


Abstract

A method for the molecular mapping of formalin-fixed, paraffin-embedded human hippocampal tissue affected by Alzheimer's disease (AD) is presented. This approach utilizes imaging mass spectrometry (IMS) with matrix-assisted laser desorption/ionization (MALDI). The usefulness of this technique in comparing diseased versus nor mal tissue at the molecular level while continuing to maintain topological and morphological integrity is evident in the preliminary findings. The critical correlation of the deparaffination, washing, matrix deposition, and analysis steps in handling the tissue sections and how these steps impact the successful mapping of human hippocampal tissue is clearly demonstrated. By use of this technique we have been able to identify several differences between the hippocampal AD tissue and the control hippocampal tissue. From the observed peptide clip masses we present preliminary identifications of the amyloid-beta peptides known to be prominent in the brains of those with AD. We have obtained high-resolution mass spectra and mass images with 100μm spatial resolution. Future experiments will couple this work with MALDI LIFT experiments to enable top down proteomics of fresh frozen tissue, which is not possible with paraffin-embedded tissues.

Keywords: Alzheimer's disease, Amyloid-beta, Hippocampal tissue, MALDI imaging, Paraffin embedded tissue.