Prion infection of mice transgenic for human APPSwe: increased accumulation of cortical formic acid extractable Abeta(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 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.
Baier
Michael
M
Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany. baierm@rki.de
Apelt
Jenny
J
Riemer
Constanze
C
Gültner
Sandra
S
Schwarz
Anja
A
Bamme
Theresa
T
Burwinkel
Michael
M
Schliebs
Reinhard
R
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005561:Formates / Q000737:chemistry; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009448:Neurochemistry / Q000379:methods; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015996:Survival Rate; D015854:Up-Regulation / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005561:Formates; D010446:Peptide Fragments; D018620:PrPSc Proteins; D011328:Prions; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C030544:formic acid