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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / genetics
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Alzheimer Disease / metabolism*
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / chemistry
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Amyloid beta-Peptides / genetics
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Protein Precursor / genetics
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Cerebral Cortex / metabolism*
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Cerebral Cortex / pathology
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Cerebral Cortex / physiopathology
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Formates / chemistry
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Gliosis / genetics
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Gliosis / metabolism
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Gliosis / pathology
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Humans
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Mice
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Mice, Transgenic
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Nerve Degeneration / genetics
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Nerve Degeneration / metabolism
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Nerve Degeneration / physiopathology
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Neurochemistry / methods
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / metabolism*
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Plaque, Amyloid / genetics
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Plaque, Amyloid / metabolism
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Plaque, Amyloid / pathology
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PrPSc Proteins / genetics
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PrPSc Proteins / metabolism
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Prion Diseases / genetics
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Prion Diseases / metabolism
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Prion Diseases / physiopathology
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Prions / metabolism*
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Scrapie / genetics
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Scrapie / metabolism*
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Scrapie / physiopathology
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Survival Rate
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Up-Regulation / genetics
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Formates
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Peptide Fragments
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PrPSc Proteins
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Prions
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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formic acid