Ibrahim Kaya (Presenter)
University of Gothenburg
Bio: I was trained and educated as an analytical chemist. I obtained my bachelors degree studying both at Institute of Chemical Technology, Prague and Izmir Institute of Technology. I did my first research on transition metal catalyzed organic reactions as graduation project and summer research project. I obtained my masters degree with a project focused on detection of the cisplatin-binding proteins by laser plasma spectroscopy prior to mass spectrometry analysis. As a visiting master of science student at Swedish National Center for Imaging Mass Spectrometry I did another project on MALDI imaging mass spectrometry analysis of neuropeptides.A few months ago I started my PhD studies under supervision of Andrew Ewing and Jörg Hanrieder at University of Gothenburg. Here I am developing and applying novel imaging mass spectrometry methods for neurodegenerative diseases.
Authorship: Ibrahim Kaya(1,2), Wojciech Michno(1), Yasmine Iacone(1), Dimitri Brinet(1,2), Stina Syvänen(4), Jörg Hanrieder(1,3,5)
1 Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden 2 Deparment of Chemistry and Molecular Biology, University of Gothenburg, Sweden 3 Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, S
| Short Abstract A number of biochemical and clinical studies suggest that in addition to peptides, dysregulated lipid metabolism may also linked to the Alzheimers disease (AD) pathogenesis. Here, gangliosides were identified to bind to Amyloid-β peptides and thereby promote fibrillogenesis. Moreover, hypercholesterolemia was found to accelerate the AD pathology. Here, we performed MALDI imaging, to study the lipid microenvironment around cortical and hippocampal Amyloid-β plaques in transgenic AD mice carrying the Arctic and Swedish mutation of amyloid-beta precursor protein (tgArcSwe). The results show distinct localization patterns of ganglioside and other biogenic lipid species to Amyloid-β pathology, suggesting a prominent role of neuronal lipid species in AD pathogenesis. |
Long Abstract
Alzheimer's disease (AD) is a chronic, neurodegenerative disorder which is characterized by the formation of amyloid-β plaques.1 Amyloid-β peptides rapidly aggregates to form oligomers, protofibrils and fibrils leading to the deposition of amyloid peptides into different extracellular (senile) deposits. In recent years genetically altered mouse models played a major role to probe the pathological mechanisms of AD.2 A number of biochemical and clinical studies suggest that in addition to peptides, dysregulated lipid metabolism may also linked to the AD pathogenesis.3 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 functional brain lipid species in situ.
Several studies have been reported about gangliosides binding to the Amyloid-β peptides, which serves as a seed for fibrillogenesis4, and hypercholesterolemia accelerates the AD pathology5. Hence, to gain comprehensive insight in spatiotemporal lipid changes in situ is essential to dissect the functional role of individual lipid species in AD pathogenesis.
MALDI imaging mass spectrometry is an advanced technique to reveal the spatial distribution maps of lipids, peptides and proteins in neuroscience.6 Previously, we have probed Amyloid-β peptide pathology in transgenic Alzheimer's disease mice7 carrying the Arctic and Swedish mutation of amyloid-beta precursor protein (tgArcSwe).8 In the present study MALDI imaging mass spectrometry was used to elucidate the lipid chemical environment around cortical and hippocampal Amyloid-β plaques in the same transgenic AD model system (tgArcSwe). 1,5-Diaminonaphthalene was used as MALDI matrix compound which yields high quality signals for both positive and negative ion lipid species.9 We used sublimation as a method for matrix application which allows high spatial resolution (down to 10μm) imaging of lipids on the brain tissue sections and identified the lipid species around the Amyloid-β plaques. The results show distinct localization patterns of ganglioside and other biogenic lipid species to Amyloid-β pathology.
References & Acknowledgements:
1.Hardy, J. A.; Higgins, G. A., Alzheimer's disease: the amyloid cascade hypothesis. Science 1992, 256 (5054), 184.
2.Morrissette, D. A.; Parachikova, A.; Green, K. N.; LaFerla, F. M., Relevance of transgenic mouse models to human Alzheimer disease. Journal of Biological Chemistry 2009, 284 (10), 6033-6037.
3.Hirsch-Reinshagen, V.; Burgess, B. L.; Wellington, C. L., Why lipids are important for Alzheimer disease? Molecular and cellular biochemistry 2009, 326 (1-2), 121-129.
4.Yamamoto, N.; Matsubara, E.; Maeda, S.; Minagawa, H.; Takashima, A.; Maruyama, W.; Michikawa, M.; Yanagisawa, K., A Ganglioside-induced Toxic Soluble Aβ Assembly ITS ENHANCED FORMATION FROM AβBEARING THE ARCTIC MUTATION. Journal of Biological Chemistry 2007, 282 (4), 2646-2655.
5.Refolo, L. M.; Pappolla, M. A.; Malester, B.; LaFrancois, J.; Bryant-Thomas, T.; Wang, R.; Tint, G. S.; Sambamurti, K.; Duff, K., Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiology of disease 2000, 7 (4), 321-331.
6.Hanrieder, J. r.; Phan, N. T.; Kurczy, M. E.; Ewing, A. G., Imaging mass spectrometry in neuroscience. ACS chemical neuroscience 2013, 4 (5), 666-679.
7.Carlred, L.; Michno, W.; Kaya, I.; Sjövall, P.; Syvänen, S.; Hanrieder, J., Probing Amyloid‐β Pathology in transgenic Alzheimer's disease (tgArcSwe) mice using MALDI Imaging Mass Spectrometry. Journal of Neurochemistry 2016.
8.Nilsberth, C.; Westlind-Danielsson, A.; Eckman, C. B.; Condron, M. M.; Axelman, K.; Forsell, C.; Stenh, C.; Luthman, J.; Teplow, D. B.; Younkin, S. G., The'Arctic'APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation. Nature neuroscience 2001, 4 (9), 887-893.
9.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.
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