Abstract
Recent technical advances in mass spectrometry, as applied to the analytical chemistry of lipid molecules, enable the simultaneous detection of the multiplicity of lipid complex species present in the human brain. This, in combination with quantitative studies carried out in plasma samples, helps to identify disease biomarkers including for Alzheimer’s disease (AD). Mass spectrometry imaging (MSI) is particularly powerful for the anatomical localization of lipids in brain slices, identifying lipid modifications in postmortem frozen samples from AD patients.
Human brain tissues are sectioned in a cryostat and then covered with a chemical matrix, such as mercaptobenzothiazole (MBT) or α-cyano-4-hydroxycinnamic acid (CHCA), to ionize the lipid molecules either by sublimation or by spraying. We describe the use of matrix-assisted laser desorption ionization (MALDI) in an LTQ–Orbitrap–XL mass spectrometer to scan brain tissue slices with high spatial resolution, analyzing 50 μm cell layers. The lipid spectra obtained for each pixel are transformed to color-coded intensity maps of hundreds of lipid species included those within a single tissue slice.
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Acknowledgments
This work was supported by the Department of Education of the Basque Government (Grant #IT1454-22 to the “Neurochemistry and Neurodegeneration” Consolidated Research group) and the ISCIII Spanish Ministry for Health (#PI20/00153) co-funded by ERDF “A way to make Europe”. Technical support and personnel, provided by General Research Services (SGiker), University of the Basque Country (UPV/EHU), the Ministry of Economy and Competitiveness (MINECO), the Basque Government, the European Regional Development Fund (ERDF), and the European Social Fund (ESF) are gratefully acknowledged. J.M.-G. is the recipient of Margarita Salas fellowship funded by the European Union-Next GenerationEU.
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Martínez-Gardeazabal, J., Moreno-Rodríguez, M., de San Román, E.G., Abad, B., Manuel, I., Rodríguez-Puertas, R. (2023). Mass Spectrometry for the Advancement of Lipid Analysis in Alzheimer’s Research. In: Chun, J. (eds) Alzheimer’s Disease. Methods in Molecular Biology, vol 2561. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2655-9_13
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DOI: https://doi.org/10.1007/978-1-0716-2655-9_13
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