Fachbereich Veterinärmedizin



    Prion infection of mice transgenic for human APPSwe:
    increased accumulation of cortical formic acid extractable Abeta(1-42) and rapid scrapie disease development (2008)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Baier, Michael
    Apelt, Jenny
    Riemer, Constanze
    Gültner, Sandra
    Schwarz, Anja
    Bamme, Theresa
    Burwinkel, Michael
    Schliebs, Reinhard
    International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience; 26(7) — S. 821–824
    ISSN: 0736-5748
    DOI: 10.1016/j.ijdevneu.2008.07.001
    Pubmed: 18662767
    Institut für Immunologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
    +49 30 838 51834

    Abstract / Zusammenfassung

    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.