Modulation of amyloid β-protein clearance and Alzheimer’s disease susceptibility by the LDL receptor–related protein pathway
The journal of clinical investigation. Bd. 106. H. 9. Ann Arbor, Mich.: American Society for Clinical Investigation 2000 S. 1159 - 1166
Erscheinungsjahr: 2000
ISBN/ISSN: 0021-9738
Publikationstyp: Zeitschriftenaufsatz
Sprache: Englisch
Doi/URN: 10.1172/JCI11013
| Geprüft: | Bibliothek |
Inhaltszusammenfassung
Susceptibility to Alzheimer's disease (AD) is governed by multiple genetic factors. Remarkably, the LDL receptor-related protein (LRP) and its ligands, apoE and alpha 2M, are all genetically associated with AD. In this study, we provide evidence for the involvement of the LRP pathway in amyloid deposition through sequestration and removal of soluble amyloid beta -protein (A beta). We demonstrate in vitro that LRP mediates the clearance of both A beta 40 and A beta 42 through a bona fide recep...Susceptibility to Alzheimer's disease (AD) is governed by multiple genetic factors. Remarkably, the LDL receptor-related protein (LRP) and its ligands, apoE and alpha 2M, are all genetically associated with AD. In this study, we provide evidence for the involvement of the LRP pathway in amyloid deposition through sequestration and removal of soluble amyloid beta -protein (A beta). We demonstrate in vitro that LRP mediates the clearance of both A beta 40 and A beta 42 through a bona fide receptor-mediated uptake mechanism. In vivo, reduced LRP expression is associated with LRP genotypes and is correlated with enhanced soluble A beta levels and amyloid deposition. Although LRP has been proposed to be a clearance pathway for A beta, this work provides the first in vivo evidence that the LRP pathway may modulate A beta deposition and AD susceptibility by regulating the removal of soluble A beta.» weiterlesen» einklappen
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Medizin
