Amyloid efflux transporter expression at the blood-brain barrier declines in normal aging.
J Neuropathol Exp Neurol
; 69(10): 1034-43, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20838242
Reduced clearance of amyloid ß peptides (Aß) across the blood-brain barrier contributes to amyloid accumulation in Alzheimer disease. Amyloid ß efflux transport is via the endothelial low-density lipoprotein receptor-related protein 1 (LRP-1) and P-glycoprotein (P-gp), whereas Aß influx transport is via the receptor for advanced glycation end products. Because age is the major risk factor for developing Alzheimer disease, we measured LRP-1 and P-gp expression and associated transporter expression with Aß accumulation in aging rats. Quantitative LRP-1 and P-gp microvessel expression was measured by immunohistochemistry (IHC); LRP-1 and P-gp expression were assessed in microvessel isolates by Western blotting. There was an age-dependent loss of capillary LRP-1 across all ages (3-36 months) by IHC (linear trend p = 0.0004) and between 3 and 20 months by Western blotting (linear trend p < 0.0001). There was a late (30-36 months) P-gp expression loss by IHC (p < 0.05) and Western blotting (p = 0.0112). Loss of LRP-1 correlated with Aß42 accumulation (p = 0.0121) and very nearly with Aß40 (p = 0.0599) across all ages. Expression of LRP-1 correlated negatively with the expression of receptor for advanced glycation end products (p < 0.0004). These data indicate that alterations in LRP-1 and P-gp expression seem to contribute progressively to Aß accumulation in aging.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Envejecimiento
/
Regulación de la Expresión Génica
/
Barrera Hematoacuosa
/
Amiloide
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido