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

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 PrPSc were identical in infected Tg2576-mice and non-transgenic littermate controls. To analyze the effect of prion infection on APP processing and generation of P-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 A beta ( 1-42) levels were 10-fold higher in infected versus Uninfected Tg2576 mice whereas other forms of A beta 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 A beta(1-42) in Tg2576 mice. (C) 2008 ISDN. Published by Elsevier Ltd. All rights reserved.