dc.contributor.author | Kaya, Ibrahim | |
dc.date.accessioned | 2020-05-18T13:43:18Z | |
dc.date.available | 2020-05-18T13:43:18Z | |
dc.date.issued | 2020-05-18 | |
dc.identifier.isbn | ISBN 978-91-7833-918-1 (PRINT) | |
dc.identifier.isbn | ISBN 978-91-7833-919-8 (PDF) | |
dc.identifier.uri | http://hdl.handle.net/2077/63614 | |
dc.description.abstract | Alzheimer’s disease (AD) is the most prevalent cause of neurodegenerative
dementia. Aggregation of amyloid β (Aβ) peptides into extracellular Aβ
plaques is one of the major neuropathological features of AD. However,
Aloysius Alzheimer reported remarkable lipid granule accumulations in
multiple glial cell types and intense lipid granules in the plaque core in AD
brain along with the proteopathic features of AD in his initial reports. While
the role of lipids in AD has until recently not received as much attention, a
body of molecular, immune, genetical, biochemical evidence closely links
aberrant lipid metabolism to several stages of AD pathogenesis. Therefore,
plaque-associated lipid molecular information in specific brain regions would
be a strong asset to dissect spatial lipid biochemistry of amyloid plaques
which would also provide a basis for further investigation of cell signaling
and metabolic pathways that are disrupted in AD. This thesis represents the
development of matrix-assisted laser desorption/ionization (MALDI) mass
spectrometry imaging (MSI) methods for single-plaque resolution spatial
lipidomics across the brain tissue sections of transgenic AD mouse models.
The developed methods include “static” MALDI for high-spatial-resolution
(at 10 μm) lipid imaging using low-energy laser pulses which can be
followed by immunofluorescence imaging of the same brain tissue section,
dual polarity MALDI-MSI on the same pixel points for spatial correlation of
lipid species ionized in both negative and positive polarities and “trimodal”
MALDI-MSI which allows spatial correlation of lipid species in dual polarity
with peptide/protein species within the same brain tissue sections at 10 μm
spatial resolution. These MALDI-MSI methods in combination with
immunohistochemistry revealed plaque-associated alterations of several
phospholipids, lysophospholipids, and sphingolipids along with the Aβ
peptide truncations and leveraged the understanding of molecular, structural
and immune signatures of Aβ pathology. For instance, we observed amyloid
plaque-associated myelin lipid architecture loss, apolipoprotein E (APOE)
mediated sulfatide depletion, region-specific and long chain base specific
accumulations of monosialogangliosides, and accumulations of several
lysophospholipids in amyloid plaques in transgenic AD mouse brain.
In summary, lipids are important components of amyloid plaques and above
mentioned novel MALDI-MSI methods in combination with other modalities
have great potential for probing spatial lipid molecular pathology of amyloid
plaques which can provide novel insights into AD pathogenesis. | sv |
dc.language.iso | eng | sv |
dc.relation.haspart | Kaya, I.; Michno, W.; Brinet, D.; Iacone, Y.; Zanni, G.; Blennow, K.; Zetterberg, H.; Hanrieder, J. Histology-Compatible MALDI Mass Spectrometry Based Imaging of Neuronal Lipids for Subsequent Immunofluorescent Staining. Analytical Chemistry 2017; 89: 4685 4694. ::PMID::28318232 | sv |
dc.relation.haspart | Kaya, I.; Brinet, D.; Michno, W.; Başkurt, M.; Zetterberg, H.; Blennow, K.; Hanrieder, J. Novel Trimodal MALDI Imaging Mass Spectrometry (IMS3) at 10 μm Reveals Spatial Lipid and Peptide Correlates Implicated in Aβ Plaque Pathology in Alzheimer’s Disease. ACS Chemical Neuroscience 2017; 8: 2778-2790. ::PMID::28925253 | sv |
dc.relation.haspart | Kaya, I.; Zetterberg, H.; Blennow, K.; Hanrieder, J.
Shedding Light on the Molecular Pathology of Amyloid Plaques in Transgenic Alzheimer’s Disease Mice Using Multimodal MALDI Imaging Mass Spectrometry. ACS Chemical Neuroscience 2018; 9: 1802-1817. ::PMID::29648443 | sv |
dc.relation.haspart | Kaya, I., Jennische, E., Dunevall, J., Lange, S., Ewing, A. G., Malmberg, P., Baykal, A. T., and Fletcher, J. S. Spatial Lipidomics Reveals Region and Long Chain Base Specific Accumulations of Monosialogangliosides in Amyloid Plaques in Familial Alzheimer’s Disease Mice (5xFAD) Brain. ACS Chemical Neuroscience 2019; 11: 14-24. ::PMID::31774647 | sv |
dc.relation.haspart | Kaya, I., Jennische, E., Lange, S., Baykal, A. T., Malmberg, P., and Fletcher, J. S. Brain Region-Specific Amyloid Plaque-Associated Myelin Lipid Loss, APOE Deposition and Disruption of the Myelin Sheath in Familial Alzheimer's Disease Mice. Journal of Neurochemistry 2020. ::PMID::32141089 | sv |
dc.subject | Alzheimer's disease | sv |
dc.subject | Lipids | sv |
dc.subject | Amyloid plaques | sv |
dc.subject | Mass spectrometry imaging | sv |
dc.subject | MALDI | sv |
dc.subject | Trimodal MALDI | sv |
dc.subject | Static MALDI | sv |
dc.subject | Dual polarity MALDI-MSI on the same pixel points | sv |
dc.subject | Neurodegeneration | sv |
dc.subject | Immunopathology | sv |
dc.subject | Amyloid peptides | sv |
dc.subject | APOE | sv |
dc.subject | Myelin | sv |
dc.subject | Sulfatides | sv |
dc.subject | 5xFAD | sv |
dc.subject | tgSwe | sv |
dc.subject | tgArcSwe | sv |
dc.subject | APP | sv |
dc.title | Development of MALDI Mass Spectrometry Imaging Methods for Probing Spatial Lipid Biochemistry of Amyloid Plaques in Alzheimer's Disease | sv |
dc.type | text | eng |
dc.type.svep | Doctoral thesis | eng |
dc.gup.mail | ibrahim.kaya@neuro.gu.se | sv |
dc.gup.mail | ibrahimokaya@gmail.com | sv |
dc.type.degree | Doctor of Philosophy (Medicine) | sv |
dc.gup.origin | University of Gothenburg. Sahlgrenska Academy | sv |
dc.gup.department | Institute of Neuroscience and Physiology. Department of Psychiatry and Neurochemistry | sv |
dc.gup.defenceplace | Måndagen den 8 juni 2020, kl. 13.00, Hörsal KB 10:an, Chalmers Tekniska Högskola, Kemivägen 10, Göteborg. https://gu-se.zoom.us/j/69844849327 | sv |
dc.gup.defencedate | 2020-06-08 | |
dc.gup.dissdb-fakultet | SA | |