| http://purl.uniprot.org/citations/23152628 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23152628 | http://www.w3.org/2000/01/rdf-schema#comment | "Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA."xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.3987-12.2012"xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/author | "Liu C.C."xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/author | "Shinohara M."xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/author | "Bu G."xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/author | "Kanekiyo T."xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/pages | "16458-16465"xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/title | "LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-beta."xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://purl.uniprot.org/core/volume | "32"xsd:string |
| http://purl.uniprot.org/citations/23152628 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23152628 |
| http://purl.uniprot.org/citations/23152628 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23152628 |
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