Apolipoprotein E and clusterin inhibit the early phase of amyloid-ß aggregation in an in vitro model of cerebral amyloid angiopathy.
Acta Neuropathol Commun
; 7(1): 12, 2019 01 28.
Article
en En
| MEDLINE
| ID: mdl-30691533
ABSTRACT
Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid-ß (Aß) deposition, which leads to lobar hemorrhage and dementia. Biological molecules affecting the development of CAA have not been fully characterized. In this study, we performed proteome analysis of biopsied leptomeningeal and cortical vessels obtained from 6 CAA patients and 5 non-CAA patients who underwent surgery for large lobar hemorrhages. We found that 6 proteins, including Aß, apolipoprotein E (apoE), clusterin (CLU), albumin, complement C4 and vitronectin were significantly upregulated in the vessels of CAA patients as compared to non-CAA patients. ApoE and CLU were found in all CAA patients. We next examined the effects of apoE and CLU on the early phase of Aß aggregation, using a simple yet powerful in vitro model of CAA, which recapitulates the intramural periarterial drainage pathway model. We found that physiological concentrations of apoE and CLU delayed the initiation time of amyloid growth kinetics in a concentration-dependent manner. These data indicate that apoE and CLU may act as extracellular chaperones to inhibit Aß amyloid deposition in CAA.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apolipoproteínas E
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Fragmentos de Péptidos
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Encéfalo
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Péptidos beta-Amiloides
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Angiopatía Amiloide Cerebral
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Clusterina
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Acta Neuropathol Commun
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM