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Subtyping of circulating exosome-bound amyloid ? reflects brain plaque deposition.

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 ? (A?) 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 A? aggregates preferentially bind with exosomes. We thus define a population of A? as exosome-bound (A?42+?CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating A?, the exosome-bound A? measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.

SUBMITTER: Lim CZJ

PROVIDER: S-EPMC6408581 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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