Soluble Amyloid-beta Aggregates from Human Alzheimer's Disease Brains.
Sci Rep
; 6: 38187, 2016 12 05.
Article
en En
| MEDLINE
| ID: mdl-27917876
ABSTRACT
Soluble amyloid-beta (Aß) aggregates likely contribute substantially to the dementia that characterizes Alzheimer's disease. However, despite intensive study of in vitro preparations and animal models, little is known about the characteristics of soluble Aß aggregates in the human Alzheimer's disease brain. Here we present a new method for extracting soluble Aß aggregates from human brains, separating them from insoluble aggregates and Aß monomers using differential ultracentrifugation, and purifying them >6000 fold by dual antibody immunoprecipitation. The method resulted in <40% loss of starting material, no detectible ex vivo aggregation of monomeric Aß, and no apparent ex vivo alterations in soluble aggregate sizes. By immunoelectron microscopy, soluble Aß aggregates typically appear as clusters of 10-20 nanometer diameter ovoid structures with 2-3 amino-terminal Aß antibody binding sites, distinct from previously characterized structures. This approach may facilitate investigation into the characteristics of native soluble Aß aggregates, and deepen our understanding of Alzheimer's dementia.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Péptidos beta-Amiloides
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Enfermedad de Alzheimer
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Agregación Patológica de Proteínas
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Sci Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos