Subtyping of circulating exosome-bound amyloid ß reflects brain plaque deposition.
Nat Commun
; 10(1): 1144, 2019 03 08.
Article
em En
| MEDLINE
| ID: mdl-30850633
ABSTRACT
Despite intense interests in developing blood measurements of Alzheimer's disease (AD), the progress has been confounded by limited sensitivity and poor correlation to brain pathology. Here, we present a dedicated analytical platform for measuring different populations of circulating amyloid ß (Aß) proteins - exosome-bound vs. unbound - directly from blood. The technology, termed amplified plasmonic exosome (APEX), leverages in situ enzymatic conversion of localized optical deposits and double-layered plasmonic nanostructures to enable sensitive, multiplexed population analysis. It demonstrates superior sensitivity (~200 exosomes), and enables diverse target co-localization in exosomes. Employing the platform, we find that prefibrillar Aß aggregates preferentially bind with exosomes. We thus define a population of Aß as exosome-bound (Aß42+ CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating Aß, the exosome-bound Aß measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Encéfalo
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Peptídeos beta-Amiloides
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Placa Amiloide
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Exossomos
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Doença de Alzheimer
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Neurônios
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article