Developing brain organotypic slice culture to model amyloid plaque formation in vitro

Kirsty Ireland, Thomas Wishart, Rona Barron

Research output: Contribution to journalMeeting abstract


Although PrPsc is commonly found to accumulate in prion diseases it has been recently discovered that its accumulation in the form of amyloid plaques can occur in the absence of infectious prion disease. After inoculation of 101LL mice with classical P102L Gerstmann–Sträussler–Scheinker syndrome (GSS) infected brain homogenate disease transmission and vacuolation are evident despite very low or undetectable levels of PrPsc. However, following inoculation with an atypical form of P102L GSS PrP amyloid plaques form in the absence of both clinical disease and vacuolation in the brains of 101LL mice (Piccardo et al 2007).
This project aims to study the mechanisms of amyloid plaque formation in real time using brain organotypic slice cultures (OSC) from a range of genetically modified mice including; 101LL, Tga20 (overexpressing PRNP), J20 (expressing human Alzheimer precursor protein with the double Swedish/Indiana mutation), GPI negative (model without glycosylphosphatidylinositol anchoring PrP to the cell membrane)and PrP null models. LI-COR Odyssey and confocal imaging systems will be utilised to visualise plaque formation in brain OSCs following exposure to infectious prion disease or recombinant PrP amyloid seeds. By exposing J20 slices to PrP amyloid seeds it will be revealed if plaque formation may be enhanced or accelerated based on conformation of the misfolded protein alone rather than the sequence.
The brain OSC will also be tested for prion infectivity levels to investigate the role of amyloid plaques in prion disease. To assess the effect of plaques on cell survival cell viability will also be tested. Brain OSCs from wild type mice have been established and characterised in culture for 8 months. Cells of the brain OSC have been investigated using a range of markers including those for viability, nuclei, stress, neurons and glia.
Original languageEnglish
Pages (from-to)18
Issue numberSuppt.
Publication statusPublished - 27 May 2014
EventPrion 2014 - Trieste, Italy, United Kingdom
Duration: 24 May 201430 Jun 2014


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