title: Simultaneous imaging of amyloid-β and lipids in brain tissue using antibody-coupled liposomes and time-of-flight secondary ion mass spectrometry.
abstract: The spatial localization of amyloid-β peptide deposits, the major component of senile plaques in Alzheimer's disease (AD), was mapped in transgenic AD mouse brains using time-of-flight secondary ion mass spectrometry (ToF-SIMS), simultaneously with several endogenous molecules that cannot be mapped using conventional immunohistochemistry imaging, including phospholipids, cholesterol and sulfatides. Whereas the endogenous lipids were detected directly, the amyloid-β deposits, which cannot be detected as intact entities with ToF-SIMS because of extensive ion-induced fragmentation, were identified by specific binding of deuterated liposomes to antibodies directed against amyloid-β. Comparative investigation of the amyloid-β deposits using conventional immunohistochemistry and fluorescence microscopy suggests similar sensitivity but a more surface-confined identification due to the shallow penetration depth of the ToF-SIMS signal. The recorded ToF-SIMS images thus display the localization of lipids and amyloid-β in a narrow (~10 nm) two-dimensional plane at the tissue surface. As compared to a frozen nontreated tissue sample, the liposome preparation protocol generally increased the signal intensity of endogenous lipids, likely caused by matrix effects associated with the removal of salts, but no severe effects on the tissue integrity and the spatial distribution of lipids were observed with ToF-SIMS or scanning electron microscopy (SEM). This method may provide an important extension to conventional tissue imaging techniques to investigate the complex interplay of different kinds of molecules in neurodegenerative diseases, in the same specimen. However, limitations in target accessibility of the liposomes as well as unspecific binding need further consideration.
authors.affiliation: Chemistry, Materials and Surfaces, SP Technical Research Institute of Sweden , P.O. Box 857, SE-501 15 Borås, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Carlred
authors.forename: Anders
authors.initials: A
authors.lastname: Gunnarsson
authors.forename: Santiago
authors.initials: S
authors.lastname: Solé-Domènech
authors.forename: Björn
authors.initials: B
authors.lastname: Johansson
authors.forename: Vladana
authors.initials: V
authors.lastname: Vukojević
authors.forename: Lars
authors.initials: L
authors.lastname: Terenius
authors.forename: Alina
authors.initials: A
authors.lastname: Codita
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Fredrik
authors.initials: F
authors.lastname: Höök
authors.forename: Peter
authors.initials: P
authors.lastname: Sjövall
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D001921:Brain / Q000648:ultrastructure*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D018629:Spectrometry, Mass, Secondary Ion
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D008055:Lipids; D008081:Liposomes