Detection of Aβ plaque-associated astrogliosis in Alzheimer’s disease brain by spectroscopic imaging and immunohistochemistry
Detection of amyloid beta plaque-associated astrogliosis in Alzheimer’s disease brain by spectroscopic imaging and immunohistochemistry.pdf (1.443Mb) Detection of amyloid beta plaque-associated astrogliosis in Alzheimer’s disease brain by spectroscopic imaging and immunohistochemistry_SI.pdf (1.069Mb)
Royal Society of Chemistry
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Recent work using micro-Fourier transform infrared (μFTIR) imaging has revealed that a lipid-rich layer surrounds many plaques in post-mortem Alzheimer's brain. However, the origin of this lipid layer is not known, nor is its role in the pathogenesis of Alzheimer's disease (AD). Here, we studied the biochemistry of plaques in situ using a model of AD. We combined FTIR, Raman and immunofluorescence images, showing that astrocyte processes co-localise with the lipid ring surrounding many plaques. We used μFTIR imaging to rapidly measure chemical signatures of plaques over large fields of view, and selected plaques for higher resolution analysis with Raman microscopy. Raman maps showed similar lipid rings and dense protein cores as in FTIR images, but also revealed cell bodies. We confirmed the presence of plaques using amylo-glo staining, and detected astrocytes using immunohistochemistry, revealing astrocyte co-localisation with lipid rings. This work is important because it correlates biochemical changes surrounding the plaque with the biological process of astrogliosis.
This work was generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA). The animals were supplied by Glaxo Smith Kline, as part of the European Union PharmacogIMI consortium. F.T. and J.H. were supported by an Alzheimer’s Society fellowship.
This is the author accepted manuscript. The final version is available from Royal Society of Chemistry via the DOI in this record.
Vol. 143, pp. 850-857