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• W2027080434 endingPage "9240" @default.
• W2027080434 startingPage "9228" @default.
• W2027080434 abstract "In addition to the fundamental role of the extracellular glycoprotein Reelin in neuronal development and adult synaptic plasticity, alterations in Reelin-mediated signaling have been suggested to contribute to neuronal dysfunction associated with Alzheimer's disease (AD). In vitro data revealed a biochemical link between Reelin-mediated signaling, Tau phosphorylation, and amyloid precursor protein (APP) processing. To directly address the role of Reelin in amyloid-beta plaque and Tau pathology in vivo, we crossed heterozygous Reelin knock-out mice (reeler) with transgenic AD mice to investigate the temporal and spatial AD-like neuropathology. We demonstrate that a reduction in Reelin expression results in enhanced amyloidogenic APP processing, as indicated by the precocious production of amyloid-beta peptides, the significant increase in number and size of amyloid-beta plaques, as well as age-related aggravation of plaque pathology in double mutant compared with single AD mutant mice of both sexes. Numerous amyloid-beta plaques accumulate in the hippocampal formation and neocortex of double mutants, precisely in layers with strongest Reelin expression and highest accumulation of Reelin plaques in aged wild-type mice. Moreover, concentric accumulations of phosphorylated Tau-positive neurons around amyloid-beta plaques were evident in 15-month-old double versus single mutant mice. Silver stainings indicated the presence of neurofibrillary tangles, selectively associated with amyloid-beta plaques and dystrophic neurites in the entorhinal cortex and hippocampus. Our findings suggest that age-related Reelin aggregation and concomitant reduction in Reelin-mediated signaling play a proximal role in synaptic dysfunction associated with amyloid-beta deposition, sufficient to enhance Tau phosphorylation and tangle formation in the hippocampal formation in aged Reelin-deficient transgenic AD mice." @default.
• W2027080434 created "2016-06-24" @default.
• W2027080434 creator A5009581742 @default.
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• W2027080434 date "2010-07-07" @default.
• W2027080434 modified "2023-10-16" @default.
• W2027080434 title "Reduced Reelin Expression Accelerates Amyloid- Plaque Formation and Tau Pathology in Transgenic Alzheimer's Disease Mice" @default.
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• W2027080434 doi "https://doi.org/10.1523/jneurosci.0418-10.2010" @default.
• W2027080434 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6632461" @default.
• W2027080434 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20610758" @default.
• W2027080434 hasPublicationYear "2010" @default.
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