Prion infection of mice transgenic for human APP sub(Swe): increased accumulation of cortical formic acid extractable A beta (1-42) and rapid scrapie disease development

• Published in: International journal of developmental neuroscience Vol. 26; no. 7; pp. 821 - 824
• Main Authors: Baier, Michael, Apelt, Jenny, Riemer, Constanze, Gueltner, Sandra, Schwarz, Anja, Bamme, Theresa, Burwinkel, Michael, Schliebs, Reinhard
• Format: Journal Article
• Language: English
• Published: 01.11.2008
• ISSN: 0736-5748
• DOI: 10.1016/j.ijdevneu.2008.07.001

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 sub(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 super(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 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.