Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals Aβ Aggregation Dependent Anionic Lipid Accumulations and Metabolism
Journal article, 2018

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, Aβ 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 Aβ into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among Aβ plaques, including cored/compact- and diffuse, may be linked to their distinct Aβ 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 (tgAPPSwe) and was correlated to Aβ 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 Aβ structures and correlate with Aβ1-42. Further, lysophospholipids implicated in neuroinflammation were increased in all Aβ 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.

Author

W. Michno

University of Gothenburg

I. Kaya

University of Gothenburg

Sofie Nyström

Linköping University

Laurent Guerard

University of Basel

University of Gothenburg

K. P. R. Nilsson

Linköping University

Per Hammarström

Linköping University

Kaj Blennow

University of Gothenburg

Sahlgrenska University Hospital

Henrik Zetterberg

Sahlgrenska University Hospital

University of Gothenburg

UCL Institute of Neurology

Jörg Hanrieder

UCL Institute of Neurology

University of Gothenburg

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Analytical Chemistry

Analytical Chemistry

0003-2700 (ISSN) 1520-6882 (eISSN)

Vol. 90 13 8130-8138

Subject Categories

Atom and Molecular Physics and Optics

Neurology

Medical Image Processing

DOI

10.1021/acs.analchem.8b01361

More information

Latest update

11/22/2019