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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2004-10-6
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pubmed:abstractText |
Alzheimer's disease (AD) is characterized by a substantial degeneration of pyramidal neurons and the appearance of neuritic plaques and neurofibrillary tangles. Here we present a novel transgenic mouse model, APP(SL)PS1KI that closely mimics the development of AD-related neuropathological features including a significant hippocampal neuronal loss. This transgenic mouse model carries M233T/L235P knocked-in mutations in presenilin-1 and overexpresses mutated human beta-amyloid (Abeta) precursor protein. Abeta(x-42) is the major form of Abeta species present in this model with progressive development of a complex pattern of N-truncated variants and dimers, similar to those observed in AD brain. At 10 months of age, an extensive neuronal loss (>50%) is present in the CA1/2 hippocampal pyramidal cell layer that correlates with strong accumulation of intraneuronal Abeta and thioflavine-S-positive intracellular material but not with extracellular Abeta deposits. A strong reactive astrogliosis develops together with the neuronal loss. This loss is already detectable at 6 months of age and is PS1KI gene dosage-dependent. Thus, APP(SL)PS1KI mice further confirm the critical role of intraneuronal Abeta(42) in neuronal loss and provide an excellent tool to investigate therapeutic strategies designed to prevent AD neurodegeneration.
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pubmed:commentsCorrections |
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http://linkedlifedata.com/resource/pubmed/commentcorrection/15466394-9796810
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0002-9440
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pubmed:author |
pubmed-author:BayerThomas ATA,
pubmed-author:BenavidesJesúsJ,
pubmed-author:BenoitPatrickP,
pubmed-author:BlanchardVéroniqueV,
pubmed-author:BoniciBrunoB,
pubmed-author:CantonThierryT,
pubmed-author:CasasCatyC,
pubmed-author:ClarkAllanA,
pubmed-author:DelacourteAndréA,
pubmed-author:DrobecqHervéH,
pubmed-author:ItierJean-MichelJM,
pubmed-author:PradierLaurentL,
pubmed-author:RetGwenaëlleG,
pubmed-author:SchmitzChristophC,
pubmed-author:SergeantNicolasN,
pubmed-author:TrempGünterG,
pubmed-author:VingtdeuxValérieV,
pubmed-author:WirthsOliverO,
pubmed-author:van de SteegEvitaE,
pubmed-author:van der KolkNicolienN
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pubmed:issnType |
Print
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pubmed:volume |
165
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1289-300
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
|
