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Localization of cho...
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
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- Solé-Domènech, Santiago (author)
- Karolinska Institutet
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- Sjövall, Peter (author)
- RISE,SP Kemi Material och Ytor,SP Technical Research Institute Sweden, Sweden,SP – Sveriges Tekniska Forskningsinstitut / Funktionella material (KMf)
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- Vukojevic, Vladana B. (author)
- Karolinska Institutet
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- Fernando, Ruani (author)
- Institut des Neurosciences de Montpellier, France,Hop St Eloi, France
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- Codita, Alina (author)
- Karolinska Institutet
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- Salve, Sachin (author)
- Karolinska Institutet
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- Bogdanovic, Nenad E. (author)
- Karolinska Institutet
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- Mohammed, Abdul H. (author)
- Karolinska Institutet
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- Hammarström, Per (author)
- Linköpings universitet,Biokemi,Tekniska högskolan
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- Nilsson, Peter (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Laferla, Frank M. (author)
- University of California Irvine, USA,University of Calif Irvine, CA USA
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- Jacob, Stefan (author)
- Karolinska Institute, Sweden
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- Berggren, Per Olof (author)
- Karolinska Institutet
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- Gimenez-Llort, Lydia (author)
- Universitat Autonoma de Barcelona, Spain
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- Schalling, Martin (author)
- Karolinska Institutet
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- Terenius, Lars H. (author)
- Karolinska Institutet
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- Johansson, Björn (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2012-09-21
- 2013
- English.
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 125:1, s. 145-157
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Abstract
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- 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.
Keyword
- Alzheimer's disease
- Amyloid-beta
- Brain
- Cholesterol
- Glia
- Imaging
- ToF-SIMS
- amyloid beta protein
- cell protein
- glial fibrillary acidic protein
- protein Iba1
- unclassified drug
- Alzheimer disease
- animal experiment
- animal model
- animal tissue
- article
- brain level
- cellular distribution
- confocal laser microscopy
- controlled study
- glia cell
- hippocampus
- immunofluorescence
- immunohistochemistry
- immunoreactivity
- lipid analysis
- lipid storage
- molecular imaging
- mouse
- nonhuman
- priority journal
- protein analysis
- protein localization
- protein structure
- scanning electron microscopy
- time of flight mass spectrometry
- time of flight secondary ion mass spectrometry
- Amyloid
- Animals
- Disease Models
- Animal
- Fluorescent Antibody Technique
- Humans
- Mice
- Mice
- 129 Strain
- Mice
- Inbred C57BL
- Mice
- Transgenic
- Neuroglia
- Neurons
- Spectrometry
- Mass
- Secondary Ion
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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Solé-Domènech, S ...
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Sjövall, Peter
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Vukojevic, Vlada ...
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Fernando, Ruani
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Codita, Alina
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Salve, Sachin
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Bogdanovic, Nena ...
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Mohammed, Abdul ...
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Hammarström, Per
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Nilsson, Peter
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Laferla, Frank M ...
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Jacob, Stefan
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Berggren, Per Ol ...
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Gimenez-Llort, L ...
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Schalling, Marti ...
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Terenius, Lars H ...
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Johansson, Björn
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- Articles in the publication
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Acta Neuropathol ...
- By the university
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RISE
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Linköping University
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Karolinska Institutet