Abstract
Expression levels of amyloid beta (Abeta)-degrading enzymes, insulin degrading enzyme (IDE) and neprilysin (NEP), were examined in transgenic mice with Alzheimer's disease-like neuropathology. After the development of first Abeta plaques in transgenic mice brain, cortical mRNA and protein levels of IDE were significantly up-regulated in the transgenic mice compared to their non-transgenic littermates. Up-regulation of IDE mRNA-levels occurred in parallel with increased Abeta40 and Abeta42 production. Additionally, a significant positive correlation was observed between protein levels of IDE and full-length amyloid precursor protein (APP) in the cerebral cortex. mRNA and protein levels of NEP were also nominally up-regulated in Tg mice compared to controls. These data may reflect up-regulation of the IDE and possibly of NEP expression in response to the Abeta accumulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / enzymology*
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Alzheimer Disease / genetics
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Cerebral Cortex / enzymology*
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Cerebral Cortex / pathology
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Cerebral Cortex / physiopathology
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Disease Models, Animal
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Gene Expression Regulation, Enzymologic / genetics
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Humans
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Insulysin / genetics
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Insulysin / metabolism*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Transgenic
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Neprilysin / genetics
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Neprilysin / metabolism
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Peptide Fragments / metabolism
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Plaque, Amyloid / enzymology*
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Plaque, Amyloid / genetics
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RNA, Messenger / metabolism
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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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Peptide Fragments
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RNA, Messenger
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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Neprilysin
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Insulysin