Prion infection of mice transgenic for human APPSwe: increased accumulation of cortical formic acid extractable Abeta(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
Source: PubMed

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.