| Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models. | |
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MedLine Citation:
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PMID: 16421297 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nerve cells that re-enter a cell cycle will die rather than divide, a fact that likely underlies the neurodegeneration in Alzheimer's disease (AD). Several mouse models of familial AD have been created, and although many display amyloid plaques in their brains, none captures the extensive pattern of nerve cell death found in the human disease. Using both immunocytochemistry and fluorescent in situ hybridization, we show that neurons in three different mouse models reproduce the ectopic cell cycling found in human AD. The temporal and spatial appearance of the cell cycle events in the mouse closely mimics the human disease progression. The cell-cycle events are evident 6 months before the first amyloid deposits and significantly precede the appearance of the first CD45+ microglia. These data suggest that the ectopic initiation of cell-cycle processes in neurons is an early sign of neuronal distress in both human and mouse AD. The close phenotypic correspondence indicates a previously unsuspected level of fidelity of the mouse model to the human disease. Finally, the relative timing suggests that neither the activated microglia nor the amyloid plaques themselves are necessary to initiate the pathogenic events in AD. |
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Authors:
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Yan Yang; Nicholas H Varvel; Bruce T Lamb; Karl Herrup |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 26 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2006 Jan |
Date Detail:
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Created Date: 2006-01-19 Completed Date: 2006-02-15 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 775-84 Citation Subset: IM |
Affiliation:
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Department of Neurology, University Hospitals of Cleveland, Cleveland, Ohio 44106, USA. yxy33@case.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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genetics*,
metabolism,
pathology Amyloid beta-Protein Precursor / biosynthesis, genetics* Animals Cell Cycle / genetics* Cell Cycle Proteins / biosynthesis, genetics* Disease Models, Animal* Humans Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic |
| Grant Support | |
ID/Acronym/Agency:
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AG023012/AG/NIA NIH HHS; AG08012/AG/NIA NIH HHS; NS20591/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Protein Precursor; 0/Cell Cycle Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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