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Multimodal Chemical...
Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A beta Aggregation Dependent Anionic Lipid Accumulations and Metabolism
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- Michno, Wojciech, 1992 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,University of Gothenburg,Univ Gothenburg, Sweden
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- Kaya, Ibrahim (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,University of Gothenburg,Univ Gothenburg, Sweden
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- Nyström, Sofie (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Guerard, Laurent (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Universität Basel,University of Basel,University of Gothenburg,Univ Gothenburg, Sweden; Univ Basel, Switzerland
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- Nilsson, Peter (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Hammarström, Per (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital,University of Gothenburg,Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital,University College London (UCL),University of Gothenburg,Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL, England
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- Hanrieder, Jörg, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,University College London (UCL),University of Gothenburg,Chalmers tekniska högskola,Chalmers University of Technology,Univ Gothenburg, Sweden; UCL, England; Chalmers Univ Technol, Sweden
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(creator_code:org_t)
- 2018-06-01
- 2018
- English.
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 90:13, s. 8130-8138
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimer's disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, A beta deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric A beta into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among A beta plaques, including cored/compact- and diffuse, may be linked to their distinct A beta profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPP(Swe)) and was correlated to A beta profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localize to the diffuse A beta structures and correlate with A beta 1-42. Further, lysophospholipids implicated in neuroinflammation were increased in all A beta deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- NATURVETENSKAP -- Fysik -- Atom- och molekylfysik och optik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences -- Atom and Molecular Physics and Optics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Medicinteknik -- Medicinsk bildbehandling (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Medical Engineering -- Medical Image Processing (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- immunoprecipitation-mass-spectrometry
- alzheimers-disease
- microglial
- response
- cerebrospinal-fluid
- apolipoprotein-e
- transgenic mice
- diffuse plaques
- protein smsr
- mouse model
- ceramide
- Chemistry
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Michno, Wojciech ...
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Kaya, Ibrahim
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Nyström, Sofie
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Guerard, Laurent
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Nilsson, Peter
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Hammarström, Per
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Blennow, Kaj, 19 ...
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Zetterberg, Henr ...
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Hanrieder, Jörg, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Physical Science ...
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and Atom and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Medical Engineer ...
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and Medical Image Pr ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Analytical Chemi ...
- By the university
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University of Gothenburg
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Chalmers University of Technology
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Linköping University