Abstract:
:To study the role of Abeta amyloid deposits in the generation of cytoskeletal lesions, we have generated a transgenic mouse line coexpressing in the same neurons a wild-type human tau isoform (0N3R), a mutant form of APP (751SL) and a mutant form of PS1 (M146L). These mice developed early cerebral extracellular deposits of Abeta, starting at 2.5 months. A somatodendritic neuronal accumulation of transgenic tau protein was observed in tau only and in tau/PS1/APP transgenic mice, including in neurons adjacent to Abeta deposits. The phosphorylation status of this somatodendritic tau was similar in the two transgenic lines. The Abeta deposits were surrounded by a neuritic reaction composed of axonal dystrophic processes, immunoreactive for many phosphotau epitopes and for the human tau transgenic protein. Ultrastructural observation showed in these dystrophic neurites a disorganisation of the microtubule and the neurofilament network but animals that were observed up to 18 months of age did not develop neurofibrillary tangles. These results indicate that overexpression of mutant PS1, mutant APP and of wild-type human tau were not sufficient per se to drive the formation of neurofibrillary tangles in a transgenic model. The Abeta deposits, however, were associated to marked changes in cytoskeletal organisation and in tau phosphorylation in adjacent dystrophic neurites.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Boutajangout A,Authelet M,Blanchard V,Touchet N,Tremp G,Pradier L,Brion JPdoi
10.1016/j.nbd.2003.09.007keywords:
subject
Has Abstractpub_date
2004-02-01 00:00:00pages
47-60issue
1eissn
0969-9961issn
1095-953Xpii
S0969996103001967journal_volume
15pub_type
杂志文章abstract::Parkinson's disease (PD), characterized by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease which produces bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (L-Dopa) is the most effective treatment for the amelioration of PD signs an...
journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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doi:10.1016/j.nbd.2018.12.022
更新日期:2019-04-01 00:00:00
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
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journal_title:Neurobiology of disease
pub_type: 杂志文章
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.05.021
更新日期:2005-12-01 00:00:00
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
pub_type: 杂志文章
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.02.011
更新日期:2010-06-01 00:00:00
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journal_title:Neurobiology of disease
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doi:10.1016/j.nbd.2012.06.026
更新日期:2012-12-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1006/nbdi.1998.0217
更新日期:1998-12-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.03.006
更新日期:2011-06-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.04.007
更新日期:2008-08-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.04.020
更新日期:2017-08-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2003.11.019
更新日期:2004-10-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2020.104957
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journal_title:Neurobiology of disease
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doi:10.1016/j.nbd.2014.06.016
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doi:10.1016/j.nbd.2011.12.022
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.08.005
更新日期:2010-12-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1998.0225
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.12.002
更新日期:2011-03-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.07.013
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) causes 10-20% of acquired epilepsy, which typically develops within 2 years post-injury with poorly understood mechanisms. We investigated the location, severity, evolution and persistence of blood-brain barrier (BBB) dysfunction and associated neuroinflammation after TBI, and th...
journal_title:Neurobiology of disease
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doi:10.1016/j.nbd.2020.105080
更新日期:2020-11-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
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更新日期:2007-06-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.12.002
更新日期:2014-03-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.03.019
更新日期:2010-10-01 00:00:00