Modulation of amyloid beta-protein clearance and Alzheimer's disease susceptibility by the LDL receptor-related protein pathway.
J Clin Invest
; 106(9): 1159-66, 2000 Nov.
Article
en En
| MEDLINE
| ID: mdl-11067868
ABSTRACT
Susceptibility to Alzheimer's disease (AD) is governed by multiple genetic factors. Remarkably, the LDL receptor-related protein (LRP) and its ligands, apoE and alpha2M, 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 (Abeta). We demonstrate in vitro that LRP mediates the clearance of both Abeta40 and Abeta42 through a bona fide receptor-mediated uptake mechanism. In vivo, reduced LRP expression is associated with LRP genotypes and is correlated with enhanced soluble Abeta levels and amyloid deposition. Although LRP has been proposed to be a clearance pathway for Abeta, this work provides the first in vivo evidence that the LRP pathway may modulate Abeta deposition and AD susceptibility by regulating the removal of soluble Abeta.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de LDL
/
Receptores Inmunológicos
/
Péptidos beta-Amiloides
/
Enfermedad de Alzheimer
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Aged80
/
Animals
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Clin Invest
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos