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Prion infection of mice transgenic for human APP Swe : increased accumulation of cortical formic acid extractable Aβ(1–42) and rapid scrapie disease development
Author(s) -
Baier Michael,
Apelt Jenny,
Riemer Constanze,
Gültner Sandra,
Schwarz Anja,
Bamme Theresa,
Burwinkel Michael,
Schliebs Reinhard
Publication year - 2008
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2008.07.001
Subject(s) - genetically modified mouse , scrapie , transgene , prion protein , gliosis , amyloid (mycology) , formic acid , biology , amyloid precursor protein , virology , microbiology and biotechnology , disease , chemistry , alzheimer's disease , pathology , medicine , biochemistry , gene , neuroscience
Neuropathological, epidemiological and experimental data indicate a potential interrelationship between Alzheimer's disease and prion diseases. Proteolytic processing of amyloid precursor protein (APP) by β‐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 β‐amyloid we determined cortical levels of SDS‐ and formic acid (FA)‐extractable forms of β‐amyloid (1–40) and (1–42) by ELISA. Formic acid‐extractable Aβ (1–42) levels were 10‐fold higher in infected versus uninfected Tg2576 mice whereas other forms of Aβ 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 Aβ(1–42) in Tg2576 mice.