{"entity": "publication", "iuid": "f0b96ae0319a4ebb931475fad35ad00b", "timestamp": "2026-04-14T08:13:03.121Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0b96ae0319a4ebb931475fad35ad00b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0b96ae0319a4ebb931475fad35ad00b"}}, "title": "Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A\u03b2 Aggregation Dependent Anionic Lipid Accumulations and Metabolism.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Nystr\u00f6m", "given": "Sofie", "initials": "S"}, {"family": "Guerard", "given": "Laurent", "initials": "L"}, {"family": "Nilsson", "given": "K Peter R", "initials": "KPR", "orcid": "0000-0002-5582-140X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c151458a1cb4a3d838c2c25d880d188.json"}}, {"family": "Hammarstr\u00f6m", "given": "Per", "initials": "P", "orcid": "0000-0001-5827-3587", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b588c389624c9ca28b0bd141cbca58.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2018-07-03", "journal": {"volume": "90", "issn": "1520-6882", "issue": "13", "pages": "8130-8138", "title": "Anal. Chem.", "issn-l": "0003-2700"}, "abstract": "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\u03b2 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\u03b2 into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among A\u03b2 plaques, including cored/compact- and diffuse, may be linked to their distinct A\u03b2 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\u03b2 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\u03b2 structures and correlate with A\u03b21-42. Further, lysophospholipids implicated in neuroinflammation were increased in all A\u03b2 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.", "doi": "10.1021/acs.analchem.8b01361", "pmid": "29856605", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:27:05.285Z", "modified": "2021-06-21T14:23:29.254Z"}