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Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A beta Aggregation Dependent Anionic Lipid Accumulations and Metabolism
Univ Gothenburg, Sweden.
Univ Gothenburg, Sweden.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
Univ Gothenburg, Sweden; Univ Basel, Switzerland.
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2018 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 13, p. 8130-8138Article in journal (Refereed) Published
Abstract [en]

Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimers 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.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2018. Vol. 90, no 13, p. 8130-8138
National Category
Biochemistry and Molecular Biology
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URN: urn:nbn:se:liu:diva-149859DOI: 10.1021/acs.analchem.8b01361ISI: 000438008600048PubMedID: 29856605OAI: oai:DiVA.org:liu-149859DiVA, id: diva2:1236438
Note

Funding Agencies|Swedish Research Council VR [20146447, 2013-2546, 2015-04521, 2017-00915]; Alzheimerfonden; Hjarnfonden; Jeanssons Stiftelsen; Ake Wiberg Stiftelse; Ahlen Stiftelsen; Stiftelsen Gamla Tjanarinnor; Torsten Soderberg Foundation; Swedish Foundation for Strategic Research; Gbran Gustafsson Foundation

Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2018-08-02

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