Cellular prion protein participates in amyloid-β transcytosis across the blood-brain barrier

被引：31
作者：
Pflanzner, Thorsten [1 ]
Petsch, Benjamin [2 ]
Andre-Dohmen, Bettina [1 ]
Mueller-Schiffmann, Andreas [3 ]
Tschickardt, Sabrina [1 ]
Weggen, Sascha [3 ]
Stitz, Lothar [2 ]
Korth, Carsten [3 ]
Pietrzik, Claus U. [1 ]
机构：
[1] Johannes Gutenberg Univ Mainz, Inst Pathobiochem, Univ Med Ctr, D-55099 Mainz, Germany
[2] Friedrich Loeffler Inst, Inst Immunol, Tubingen, Germany
[3] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany
来源：
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2012年 / 32卷 / 04期
关键词：
Alzheimer's disease; amyloid-beta; blood-brain barrier; cellular prion protein; transcytosis; RECEPTOR-RELATED PROTEIN-1; CELLS; IMPAIRMENT; CLEARANCE; PEPTIDE;
D O I：
10.1038/jcbfm.2012.7
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
The blood-brain barrier (BBB) facilitates amyloid-beta (A beta) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrPc), a putative receptor implicated in mediating A beta neurotoxicity in Alzheimer's disease (AD), participates in A beta transcytosis across the BBB. Using an in vitro BBB model, [I-125]-A beta(1-40) transcytosis was reduced by genetic knockout of PrPc or after addition of a competing PrPc-specific antibody. Furthermore, we provide evidence that PrPc is expressed in endothelial cells and, that monomeric A beta(1-40) binds to PrPc. These observations provide new mechanistic insights into the role of PrPc in AD. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 628-632; doi:10.1038/jcbfm.2012.7; published online 1 February 2012
引用
收藏
页码：628 / 632
页数：5
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