Localization of cholesterol, amyloid and glia in Alzheimer's disease transgenic mouse brain tissue using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and immunofluorescence imaging

Santiago Solé-Domènech, Peter Sjövall, Vladana Vukojević, Ruani Fernando, Alina Codita, Sachin Salve, Nenad Bogdanović, Abdul H. Mohammed, Per Hammarström, K. Peter R. Nilsson, Frank M. Laferla, Stefan Jacob, Per Olof Berggren, Lydia Giménez-Llort, Martin Schalling, Lars Terenius, Björn Johansson

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The spatial distributions of lipids, amyloid-beta deposits, markers of neurons and glial cells were imaged, at submicrometer lateral resolution, in brain structures of a mouse model of Alzheimer's disease using a new methodology that combines time-of-flight secondary ion mass spectrometry (ToF-SIMS) and confocal fluorescence microscopy. The technology, which enabled us to simultaneously image the lipid and glial cell distributions in Tg2576 mouse brain structures, revealed micrometer-sized cholesterol accumulations in hippocampal regions undergoing amyloid-beta deposition. Such cholesterol granules were either associated with individual amyloid deposits or spread over entire regions undergoing amyloidogenesis. Subsequent immunohistochemical analysis of the same brain regions showed increased microglial and astrocytic immunoreactivity associated with the amyloid deposits, as expected from previous studies, but did not reveal any particular astrocytic or microglial feature correlated with cholesterol granulation. However, dystrophic neurites as well as presynaptic vesicles presented a distribution similar to that of cholesterol granules in regions undergoing amyloid-beta accumulation, thus indicating that these neuronal endpoints may retain cholesterol in areas with lesions. In conclusion, the present study provides evidence for an altered cholesterol distribution near amyloid deposits that would have been missed by several other lipid analysis methods, and opens for the possibility to study in detail the putative liaison between lipid environment and protein structure and function in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)145-157
Number of pages13
JournalActa neuropathologica
Volume125
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Alzheimer's disease
  • Amyloid-beta
  • Brain
  • Cholesterol
  • Glia
  • Imaging
  • ToF-SIMS

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

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    Solé-Domènech, S., Sjövall, P., Vukojević, V., Fernando, R., Codita, A., Salve, S., Bogdanović, N., Mohammed, A. H., Hammarström, P., Nilsson, K. P. R., Laferla, F. M., Jacob, S., Berggren, P. O., Giménez-Llort, L., Schalling, M., Terenius, L., & Johansson, B. (2013). Localization of cholesterol, amyloid and glia in Alzheimer's disease transgenic mouse brain tissue using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and immunofluorescence imaging. Acta neuropathologica, 125(1), 145-157. https://doi.org/10.1007/s00401-012-1046-9