title: Imaging of amyloid-β in Alzheimer's disease transgenic mouse brains with ToF-SIMS using immunoliposomes.
abstract: Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been proven to successfully image different kinds of molecules, especially a variety of lipids, in biological samples. Proteins, however, are difficult to detect as specific entities with this method due to extensive fragmentation. To circumvent this issue, the authors present in this work a method developed for detection of proteins using antibody-conjugated liposomes, so called immunoliposomes, which are able to bind to the specific protein of interest. In combination with the capability of ToF-SIMS to detect native lipids in tissue samples, this method opens up the opportunity to analyze many different biomolecules, both lipids and proteins, at the same time, with high spatial resolution. The method has been applied to detect and image the distribution of amyloid-β (Aβ), a biologically relevant peptide in Alzheimer's disease (AD), in transgenic mouse brain tissue. To ensure specific binding, the immunoliposome binding was verified on a model surface using quartz crystal microbalance with dissipation monitoring. The immunoliposome binding was also investigated on tissue sections with fluorescence microscopy, and compared with conventional immunohistochemistry using primary and secondary antibodies, demonstrating specific binding to Aβ. Using ToF-SIMS imaging, several endogenous lipids, such as cholesterol and sulfatides, were also detected in parallel with the immunoliposome-labeled Aβ deposits, which is an advantage compared to fluorescence microscopy. This method can thus potentially provide further information about lipid-protein interactions, which is important to understand the mechanisms of neurodegeneration in AD.
authors.affiliation: SP Technical Research Institute of Sweden, Borås SE-501 15, Sweden and Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Carlred
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet and Center for Molecular Medicine (CMM), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Vladana
authors.initials: V
authors.lastname: Vukojević
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine (CMM), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Johansson
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine (CMM), Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.affiliation: Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Höök
authors.affiliation: SP Technical Research Institute of Sweden, Borås SE-501 15, Sweden and Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Sjövall
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000818:Animals; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008081:Liposomes; D008822:Mice, Transgenic; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides; D008081:Liposomes