Abstract：
:Transgenic mice expressing mutant human amyloid precursor protein (APP) develop an age-dependent amyloid pathology and memory deficits, but no overt neuronal loss. Here, in mice overexpressing wild-type human APP (hAPP(wt)) we found an early memory impairment, particularly in the water maze and to a lesser extent in the object recognition task, but beta-amyloid peptide (Abeta(42)) was barely detectable in the hippocampus. In these mice, hAPP processing was basically non-amyloidogenic, with high levels of APP carboxy-terminal fragments, C83 and APP intracellular domain. A tau pathology with an early increase in the levels of phosphorylated tau in the hippocampus, a likely consequence of enhanced ERK1/2 activation, was also observed. Furthermore, these mice presented a loss of synapse-associated proteins: PSD95, AMPA and NMDA receptor subunits and phosphorylated CaMKII. Importantly, signs of neurodegeneration were found in the hippocampal CA1 subfield and in the entorhinal cortex that were associated to a marked loss of MAP2 immunoreactivity. Conversely, in mice expressing mutant hAPP, high levels of Abeta(42) were found in the hippocampus, but no signs of neurodegeneration were apparent. The results support the notion of Abeta-independent pathogenic pathways in Alzheimer's disease.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Simón AM,Schiapparelli L,Salazar-Colocho P,Cuadrado-Tejedor M,Escribano L,López de Maturana R,Del Río J,Pérez-Mediavilla A,Frechilla Ddoi
10.1016/j.nbd.2008.11.005subject
Has Abstractpub_date
2009-03-01 00:00:00pages
369-78issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(08)00278-7journal_volume
33pub_type
杂志文章abstract：:The deposition and accumulation of amyloid-beta-peptide (Abeta) in the brain are considered a sine qua non for Alzheimer's disease. The experimental delivery of fibrilized Abeta serves as a cellular model for several facets of the disease including the induction of synaptic dysfunction and apoptosis. c-Abl kinase is i...
journal_title：Neurobiology of disease
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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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更新日期：2018-11-01 00:00:00
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journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2005.08.005
更新日期：2006-02-01 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：2019-12-01 00:00:00
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journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2006.03.007
更新日期：2006-08-01 00:00:00
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journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
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更新日期：2010-06-01 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：2005-06-01 00:00:00
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journal_title：Neurobiology of disease
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更新日期：2016-09-01 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：2003-12-01 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：2016-02-01 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：2004-04-01 00:00:00
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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
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journal_title：Neurobiology of disease
pub_type： 杂志文章
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更新日期：2018-04-01 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：2013-06-01 00:00:00
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journal_title：Neurobiology of disease
pub_type： 杂志文章,评审
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更新日期：2017-11-01 00:00:00
abstract：:The hippocampus is often injured in neonatal stroke. We have investigated the effect of erythropoietin (EPO) on oxygen-glucose deprived hippocampal slices and hypoxic progenitor cells. EPO improved survival of the organotypic hippocampal slices with significantly less cell death in the dentate gyrus and an increased n...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2010.01.015
更新日期：2010-05-01 00:00:00
abstract：:Failure of cell cycle regulation in neurons might be critically involved in the process of neurodegeneration in Alzheimer's disease (AD). We present here evidence to support the hypothesis that cell cycle alterations occur in cells other than neurons in AD sufferers. Lymphocytes from AD patients immortalized with Epst...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/s0969-9961(03)00040-8
更新日期：2003-08-01 00:00:00
abstract：:Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of comp...
journal_title：Neurobiology of disease
pub_type： 杂志文章
doi：10.1016/j.nbd.2019.04.004
更新日期：2019-07-01 00:00:00
