Ganglioside Detection from Formalin Fixed Human Brain Tissue Utilizing MALDI Imaging Mass Spectrometry

Abstract

Matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is largely performed on fresh frozen tissue whereas clinical tissue samples stored long term are fixed in formalin, and the fixation process is thought to cause signal suppression for lipid molecules. Studies show that fresh frozen brain tissue sections washed with ammonium formate (AF) solution prior to matrix application in the MALDI-IMS procedure display an increase in signal intensity and sensitivity for lipid molecules while maintaining molecular spatial distribution. Work in this thesis compares MALDI data of ganglioside molecules from fresh frozen and post-fixed rat brain samples, and post-fixed human brain samples washed with AF. Results demonstrate that MALDI-IMS spectra for gangliosides are significantly enhanced in fresh frozen rat brain, formalin-fixed rat brain and formalin fixed human brain samples washed with AF. This method will allow for analysis of gangliosides from formalin-fixed clinical samples, which can open additional avenues for neurodegenerative disease research

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