ATP-binding cassette transporters P-glycoprotein and breast cancer related protein are reduced in capillary cerebral amyloid angiopathy.
Neurobiol Aging
; 35(3): 565-75, 2014 Mar.
Article
en En
| MEDLINE
| ID: mdl-24138987
ABSTRACT
Alzheimer's disease (AD) is the most common form of dementia and marked by deposition of amyloid-ß (Aß) within the brain. Alterations of Aß transporters at the neurovasculature may play a role in the disease process. We investigated the expression of ABC transporters P-glycoprotein (P-gp) and breast cancer related protein (BCRP) in non-neurologic controls, AD, and severe capillary cerebral amyloid angiopathy (capCAA) cases, which are characterized by deposition of Aß within cerebral capillaries. Our data show that microvascular expression of P-gp and BCRP is strikingly decreased in capCAA-affected vessels but not in AD and control samples. Messenger RNA levels of P-gp, but not of BCRP, were downregulated in brain endothelial cells on exposure to oligomeric Aß42, but not fibrillar Aß42 or Aß40. Coincubating Aß42 together with clusterin, an amyloid-associated protein highly expressed in capCAA-affected vessels, strongly reduced levels of P-gp. In conclusion, accumulation of Aß, in combination with clusterin, within and around cerebral capillaries, may further aggravate the disease process in AD by affecting P-gp expression. Loss of P-gp expression or activity may serve as a selective biomarker for ongoing capCAA.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Capilares
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Expresión Génica
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Péptidos beta-Amiloides
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Angiopatía Amiloide Cerebral
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
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Transportadoras de Casetes de Unión a ATP
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Células Endoteliales
Tipo de estudio:
Diagnostic_studies
Límite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurobiol Aging
Año:
2014
Tipo del documento:
Article
País de afiliación:
Países Bajos