Prion-like seeding and nucleation of intracellular amyloid-ß.
Neurobiol Dis
; 113: 1-10, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29414379
ABSTRACT
Alzheimer's disease (AD) brain tissue can act as a seed to accelerate aggregation of amyloid-ß (Aß) into plaques in AD transgenic mice. Aß seeds have been hypothesized to accelerate plaque formation in a prion-like manner of templated seeding and intercellular propagation. However, the structure(s) and location(s) of the Aß seeds remain unknown. Moreover, in contrast to tau and α-synuclein, an in vitro system with prion-like Aß has not been reported. Here we treat human APP expressing N2a cells with AD transgenic mouse brain extracts to induce inclusions of Aß in a subset of cells. We isolate cells with induced Aß inclusions and using immunocytochemistry, western blot and infrared spectroscopy show that these cells produce oligomeric Aß over multiple replicative generations. Further, we demonstrate that cell lysates of clones with induced oligomeric Aß can induce aggregation in previously untreated N2a APP cells. These data strengthen the case that Aß acts as a prion-like protein, demonstrate that Aß seeds can be intracellular oligomers and for the first time provide a cellular model of nucleated seeding of Aß.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Prosencéfalo
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Placa Amiloide
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Proteínas Priônicas
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Líquido Intracelular
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article