Mass Spectrometry Imaging of Lipids: Generation of Untargeted Consensus Spectra Reveals Spatial Distributions in Niemann-Pick Disease, Type C1
Olson, Matthew T.
Cologna, Stephanie M.
PublisherAmerican Society for Biochemistry and Molecular Biology
MetadataShow full item record
Mass spectrometry imaging is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick Disease, Type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endolysosomal system. Here, we use mass spectrometry imaging to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls. To complement the imaging studies, a data processing pipeline was developed to generate consensus mass spectra thereby using both technical and biological image replicates to assess differences. The consensus spectra are used to determine true differences in lipid relative abundance; lipid distributions can be determined in an unbiased fashion without prior knowledge of location. We show the cerebellar distribution of gangliosides GM1, GM2 and GM3 including variants of lipid chain length. We also performed MALDI-MSI of cholesterol. Further analysis of lobules IV/V and X of the cerebellum gangliosides indicates regional differences. The specificity achieved highlights the power of MSI and this new workflow demonstrates a universal approach for addressing reproducibility in imaging experiments applied to NPC1.
CitationTobias, F., Olson, M. T., & Cologna, S. M. (2018). Mass spectrometry imaging of lipids: Untargeted consensus spectra reveal spatial distributions in Niemann-Pick disease type C1. Journal of Lipid Research, 59(12), 2446-2455. doi:10.1194/jlr.D086090
Niemann-Pick Disease Type C