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rdf:type |
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lifeskim:mentions |
umls-concept:C0006104,
umls-concept:C0078939,
umls-concept:C0086597,
umls-concept:C0443199,
umls-concept:C0597298,
umls-concept:C0611285,
umls-concept:C0962722,
umls-concept:C1416912,
umls-concept:C1417509,
umls-concept:C1419111,
umls-concept:C1704675,
umls-concept:C1723136,
umls-concept:C1869507,
umls-concept:C2354310
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pubmed:issue |
3
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pubmed:dateCreated |
2004-8-5
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pubmed:abstractText |
LRP (low-density lipoprotein receptor-related protein) is linked to Alzheimer's disease (AD). Here, we report amyloid beta-peptide Abeta40 binds to immobilized LRP clusters II and IV with high affinity (Kd = 0.6-1.2 nM) compared to Abeta42 and mutant Abeta, and LRP-mediated Abeta brain capillary binding, endocytosis, and transcytosis across the mouse blood-brain barrier are substantially reduced by the high beta sheet content in Abeta and deletion of the receptor-associated protein gene. Despite low Abeta production in the brain, transgenic mice expressing low LRP-clearance mutant Abeta develop robust Abeta cerebral accumulations much earlier than Tg-2576 Abeta-overproducing mice. While Abeta does not affect LRP internalization and synthesis, it promotes proteasome-dependent LRP degradation in endothelium at concentrations > 1 microM, consistent with reduced brain capillary LRP levels in Abeta-accumulating transgenic mice, AD, and patients with cerebrovascular beta-amyloidosis. Thus, low-affinity LRP/Abeta interaction and/or Abeta-induced LRP loss at the BBB mediate brain accumulation of neurotoxic Abeta.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0896-6273
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pubmed:author |
pubmed-author:DavisJudianneJ,
pubmed-author:DeaneRashidR,
pubmed-author:Du YanShiS,
pubmed-author:GEARJJ,
pubmed-author:GuoHuangH,
pubmed-author:HuHong WeiHW,
pubmed-author:LaRueBarbraB,
pubmed-author:LentingPeter JPJ,
pubmed-author:MehneDD,
pubmed-author:ParisiMargaretM,
pubmed-author:SagareAbhayA,
pubmed-author:SongXiaomeiX,
pubmed-author:SpijkersPatriciaP,
pubmed-author:Van NostrandWilliam EWE,
pubmed-author:WuZhenhuaZ,
pubmed-author:ZlokovicBerislav VBV
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pubmed:copyrightInfo |
Copyright 2004 Cell Press
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
333-44
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15294142-Amyloid beta-Peptides,
pubmed-meshheading:15294142-Animals,
pubmed-meshheading:15294142-Blood-Brain Barrier,
pubmed-meshheading:15294142-Brain,
pubmed-meshheading:15294142-Cell Line,
pubmed-meshheading:15294142-Cricetinae,
pubmed-meshheading:15294142-Humans,
pubmed-meshheading:15294142-LDL-Receptor Related Proteins,
pubmed-meshheading:15294142-Male,
pubmed-meshheading:15294142-Mice,
pubmed-meshheading:15294142-Mice, Inbred C57BL,
pubmed-meshheading:15294142-Mice, Knockout,
pubmed-meshheading:15294142-Mice, Transgenic,
pubmed-meshheading:15294142-Peptide Fragments,
pubmed-meshheading:15294142-Protein Binding,
pubmed-meshheading:15294142-Protein Isoforms
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pubmed:year |
2004
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pubmed:articleTitle |
LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms.
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pubmed:affiliation |
Frank P. Smith Laboratories for Neuroscience and Neurosurgical Research, Department of Neurosurgery, Arthur Kornberg Medical Research Building, University of Rochester Medical Center, Rochester, NY 14642, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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