Jörg Hanrieder (Presenter)
University of Gothenburg
Authorship: Yasmine Iacone(1), Ibrahim Kaya (1,2), Dimitri Brinet (1,2), Wojciech Michno (1), Jörg Hanrieder (1,3)
(1)Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden (2)Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden (3)Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden
Lipids mediated mechanisms are involved in numerous aspects of brain pathology. Genetic predisposition with the apolipoprotein E (APOE) e4 allele, a lipid transporter protein, was identified as the major risk factor to develop sporadic Alzheimer’s disease (AD), implicating a prominent role for lipids in AD pathogenesis. This requires therefore a full comprehension of the pathological and chemical changes of brain lipid species in situ. In the present project, MALDI imaging mass spectrometry has been used to determine lipids mass profile around plaques of post mortem human cortical brain from AD patients. Furthermore, sublimation with pentafluorobenzoic acid (PFBA) prior to deposition of 1,5 diaminonaphtlene (1,5 DAN) matrix was used for enhancing the signal intensity of lipid species in positive ion mode. The data show distinct lipid localizations that were correlated to AD pathology.
Alzheimer’s disease is one of the most common later-onset neurodegenerative disorders. The pathological hallmarks of the disease comprehend abnormal protein aggregation of amyloid beta peptide into extracellular compact plaques, and the hyperphosphorilation of intraneuronal tau protein.(1) Evidences suggest that lipids are as well determinant factors for the progression of the disease. Neuronal lipid species they are linked to several biochemical mechanisms involved in brain functions.(2) Moreover, genetic predisposition with the apolipoprotein E (APOE) e4 allele, a lipid transporter protein, was identified as the major risk factor to develop sporadic Alzheimer’s disease (AD), implicating a prominent role for lipids in AD pathogenesis. This requires therefore a full comprehension of the pathological and chemical changes of brain lipid species in situ.
Mass spectrometry imaging is one of the emerging techniques for the localization of different structures in biological tissues and has been fully employed to chemically and structurally characterized different lipids profiles in both positive and negative ion mode.(3) So far, lipidomics of amyloid plaques has been addressed to study the lipid changes in AD model systems including transgenic animal models or in amyloid--incubated cells.(2)
In this study, we used 1,5-diaminonaphthalene (1,5-DAN) as MALDI matrix compound which yields high quality lipid signals for both negative and positive ion mode.(4) Sublimation was used to deposit the matrix compound on cortical human brain sections which provides high spatial resolution (down to 10µm). Additionally, we used penta-fluorobenzoic acid (PFBA) sublimation prior to 1,5-DAN to enhance the signal intensity of lipids in positive ion mode. We report herein the lipids mass profile around A plaques in post mortem human cortical brain regions that were correlated to respective changes in AD pathology.
References & Acknowledgements:
(1) Blennow, K. et al. Alzheimer’s disease, Lancet, 2006, 368:387-403
(2) Ellis, S. R.; Cappell, J.; Potočnik, N. O.; Balluff, B.; Hamaide, J.; Van der Linden, A.; Heeren, R. M., More from less: high-throughput dual polarity lipid imaging of biological tissues. Analyst,2016
(3) Di Paolo, G.; Kim, T.-W., Linking lipids to Alzheimer's disease: cholesterol and beyond. Nature Reviews Neuroscience 2011, 12 (5), 284-296
(4) Thomas, A. l.; Charbonneau, J. L.; Fournaise, E.; Chaurand, P., Sublimation of new matrix candidates for high spatial resolution imaging mass spectrometry of lipids: enhanced information in both positive and negative polarities after 1, 5-diaminonapthalene deposition. Analytical chemistry 2012, 84 (4), 2048-2054
IP Royalty: no
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