Simultaneous imaging of amyloid-β and lipids in brain tissue using antibody-coupled liposomes and time-of-flight secondary ion mass spectrometry
Artikel i vetenskaplig tidskrift, 2014

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. © 2014 American Chemical Society.


Louise M Carlred

Chalmers, Teknisk fysik, Biologisk fysik

Anders Gunnarsson

Chalmers, Teknisk fysik, Biologisk fysik

S. Solé-Domènech

Weill Cornell Medical College

Lunds universitet

Karolinska Institutet

Björn Johansson Fast

Karolinska Institutet

Vladana Vukojević

Karolinska Institutet

L.T. Terenius

Karolinska Institutet

A. Codita

Karolinska Institutet

B.G. Winblad

Karolinska Institutet

Martin Schalling

Karolinska Institutet

Fredrik Höök

Chalmers, Teknisk fysik, Biologisk fysik

Peter Sjövall

Chalmers, Teknisk fysik, Biologisk fysik

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 136 28 9973-9981


Biokemi och molekylärbiologi



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