Dietetics, Nutrition and Biological Sciences
Permanent URI for this collectionhttps://eresearch.qmu.ac.uk/handle/20.500.12289/23
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Item Mechanism of PrP-Amyloid Formation in Mice Without Transmissible Spongiform Encephalopathy(Wiley, 2011-06-03) Jeffrey, Martin; McGovern, Gillian; Chambers, Emily V.; King, Declan; Gonzalez, Lorenzo; Manson, Jean C.; Ghetti, Bernardino; Piccardo, Pedro; Barron, RonaGerstmann–Sträussler–Scheinker (GSS) P102L disease is a familial form of a transmissible spongiform encephalopathy (TSE) that can present with or without vacuolation of neuropil. Inefficient disease transmission into 101LL transgenic mice was previously observed from GSS P102L without vacuolation. However, several aged, healthy mice had large plaques composed of abnormal prion protein (PrPd). Here we perform the ultrastructural characterization of such plaques and compare them with PrPd aggregates found in TSE caused by an infectious mechanism. PrPd plaques in 101LL mice varied in maturity, with some being composed of deposits without visible amyloid fibrils. PrPd was present on cell membranes in the vicinity of all types of plaques. In contrast to the unicentric plaques seen in infectious murine scrapie, the plaques seen in the current model were multicentric and were initiated by protofibrillar forms of PrPd situated on oligodendroglia, astrocytes and neuritic cell membranes. We speculate that the initial conversion process leading to plaque formation begins with membrane-bound PrPC but that subsequent fibrillization does not require membrane attachment. We also observed that the membrane alterations consistently seen in murine scrapie and other infectious TSEs were not present in 101LL mice with plaques, suggesting differences in the pathogenesis of these conditions.Item Membrane pathology and microglial activation of mice expressing membrane anchored or membrane released forms of Aβ and mutated human Alzheimer's precursor protein (APP)(Wiley, 2014-08-18) Jeffrey, Martin; McGovern, Gillian; Barron, Rona; Baumann, FrankAlzheimer's disease and the transmissible spongiform encephalopathies or prion diseases accumulate misfolded and aggregated forms of neuronal cell membrane proteins. Distinctive membrane lesions caused by the accumulation of disease-associated prion protein (PrPd) are found in prion disease but morphological changes of membranes are not associated with Aβ in Alzheimer's disease. Membrane changes occur in all prion diseases where PrPd is attached to cell membranes by a glycosyl-phosphoinositol (GPI) anchor but are absent from transgenic mice expressing anchorless PrPd. Here we investigate whether GPI membrane attached Aβ may also cause prion-like membrane lesions.