PMID- 26801213 OWN - NLM STAT- MEDLINE DCOM- 20161013 LR - 20161230 IS - 1559-4106 (Electronic) IS - 1559-4106 (Linking) VI - 11 IP - 2 DP - 2016 Jun 22 TI - Imaging of amyloid-beta in Alzheimer's disease transgenic mouse brains with ToF-SIMS using immunoliposomes. PG - 02A312 LID - 10.1116/1.4940215 [doi] AB - 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-beta (Abeta), 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 Abeta. Using ToF-SIMS imaging, several endogenous lipids, such as cholesterol and sulfatides, were also detected in parallel with the immunoliposome-labeled Abeta 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. FAU - Carlred, Louise AU - Carlred L AD - SP Technical Research Institute of Sweden, Boras SE-501 15, Sweden and Department of Applied Physics, Chalmers University of Technology, SE-412 96 Goteborg, Sweden. FAU - Vukojevic, Vladana AU - Vukojevic V AD - Department of Clinical Neuroscience, Karolinska Institutet and Center for Molecular Medicine (CMM), Karolinska University Hospital, SE-171 76 Stockholm, Sweden. FAU - Johansson, Bjorn AU - Johansson B AD - Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine (CMM), Karolinska University Hospital, SE-171 76 Stockholm, Sweden. FAU - Schalling, Martin AU - Schalling M AD - Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine (CMM), Karolinska University Hospital, SE-171 76 Stockholm, Sweden. FAU - Hook, Fredrik AU - Hook F AD - Department of Applied Physics, Chalmers University of Technology, SE-412 96 Goteborg, Sweden. FAU - Sjovall, Peter AU - Sjovall P AD - SP Technical Research Institute of Sweden, Boras SE-501 15, Sweden and Department of Applied Physics, Chalmers University of Technology, SE-412 96 Goteborg, Sweden. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20160622 PL - United States TA - Biointerphases JT - Biointerphases JID - 101275679 RN - 0 (Amyloid beta-Peptides) RN - 0 (Liposomes) SB - IM MH - Alzheimer Disease/*pathology MH - Amyloid beta-Peptides/*analysis MH - Animals MH - Brain/*pathology MH - Disease Models, Animal MH - *Immunohistochemistry MH - *Liposomes MH - Mice, Transgenic MH - Spectrometry, Mass, Secondary Ion/*methods EDAT- 2016/01/24 06:00 MHDA- 2016/10/14 06:00 CRDT- 2016/01/24 06:00 PHST- 2016/01/24 06:00 [entrez] PHST- 2016/01/24 06:00 [pubmed] PHST- 2016/10/14 06:00 [medline] AID - 10.1116/1.4940215 [doi] PST - epublish SO - Biointerphases. 2016 Jun 22;11(2):02A312. doi: 10.1116/1.4940215.