Imaging of Amyloid-β in Alzheimer’s disease transgenic mouse brains with Time-of-Flight Secondary Ion Mass Spectrometry using Immunoliposomes
Journal article, 2016

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 braintissue. 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.

immunoliposomes

cholesterol

Amyloid-beta

sulfatides

TOF-SIMS

Author

Louise M Carlred

Chalmers, Physics, Biological Physics

Vladana Vukojević

Karolinska University Hospital

Björn Johansson Fast

Karolinska University Hospital

Martin Schalling

Karolinska University Hospital

Fredrik Höök

Chalmers, Physics, Biological Physics

Peter Sjövall

Chalmers, Physics, Biological Physics

Biointerphases

1559-4106 (ISSN) 1934-8630 (eISSN)

Vol. 11 2 1-11

Areas of Advance

Nanoscience and Nanotechnology (2010-2017)

Life Science Engineering (2010-2018)

Subject Categories

Biochemistry and Molecular Biology

Analytical Chemistry

Neurosciences

Biophysics

DOI

10.1116/1.4940215

PubMed

26801213

More information

Created

10/7/2017