Amyloid ß oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes.
Science
; 365(6450)2019 07 19.
Article
em En
| MEDLINE
| ID: mdl-31221773
ABSTRACT
Cerebral blood flow is reduced early in the onset of Alzheimer's disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism. We found that in humans with cognitive decline, amyloid ß (Aß) constricts brain capillaries at pericyte locations. This was caused by Aß generating reactive oxygen species, which evoked the release of endothelin-1 (ET) that activated pericyte ETA receptors. Capillary, but not arteriole, constriction also occurred in vivo in a mouse model of AD. Thus, inhibiting the capillary constriction caused by Aß could potentially reduce energy lack and neurodegeneration in AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Capilares
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Córtex Cerebral
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Circulação Cerebrovascular
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Peptídeos beta-Amiloides
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Constrição Patológica
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Pericitos
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Doença de Alzheimer
Limite:
Animals
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Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido