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Prion infection of mice transgenic for human APPSwe: increased accumulation of cortical formic acid extractable Aβ(1-42) and rapid scrapie disease development

Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
International Journal of Developmental Neuroscience (Impact Factor: 2.92). 08/2008; 26(7):821-4. DOI: 10.1016/j.ijdevneu.2008.07.001
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ABSTRACT Neuropathological, epidemiological and experimental data indicate a potential interrelationship between Alzheimer's disease and prion diseases. Proteolytic processing of amyloid precursor protein (APP) by beta-secretase was recently suggested to be controlled by prion protein expression. Here, we characterized the prion infection of Tg2576 mice, which overexpress the human APP(Swe) protein. Prion infection of Tg2576-mice led to an early death of the animals, which was preceded by a relatively short symptomatic stage. However, disease-associated gliosis and deposition of misfolded prion protein PrP(Sc) were identical in infected Tg2576-mice and non-transgenic littermate controls. To analyze the effect of prion infection on APP processing and generation of beta-amyloid we determined cortical levels of SDS- and formic acid (FA)-extractable forms of beta-amyloid (1-40) and (1-42) by ELISA. Formic acid-extractable Abeta (1-42) levels were 10-fold higher in infected versus uninfected Tg2576 mice whereas other forms of Abeta were essentially unaffected by the prion infection. Hence, the experimental model demonstrates that a prion infection of the CNS promotes selectively formation of FA-extractable Abeta(1-42) in Tg2576 mice.

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    • "* p < 0.05, ** p < 0.005). L. Ordóñez-Gutiérrez et al. / Neurobiology of Aging 34 (2013) 2793e2804 2800 some differences in the rate of survival after prion infection in the presence/absence of APP (Baier et al., 2008), we observed no such differences when mouse have 2 or more copies of Prnp. In those cases, prion infectivity was correlated only with the presence or absence of PrP c . "
    Neurobiology of aging 01/2013; · 4.85 Impact Factor
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    • "In addition, Hooper and Turner (2008) described that PrP c inhibits BACE1-dependent APP cleavage. In contrast, other authors have indicated that PrP c increases Aβ deposition (Schwarze-Eicker et al., 2005) or that Aβ levels increase in an AD mouse model after prion inoculation (Baier et al., 2008). On the other hand, a recent study has described a relation between PrP sc type and Aβ deposition in the cerebellum of sCJD with older age at disease onset and long disease duration (Debatin et al., 2008). "
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