Subtyping of circulating exosome-bound amyloid β reflects brain plaque deposition

Carine Z. J. Lim, Yan Zhang, Yu Chen, Haitao Zhao, Mary C. Stephenson, Nicholas R. Y. Ho, Yuan Chen, Jaehoon Chung, Anthonin Reilhac, Tze Ping Loh, Christopher L. H. Chen and Huilin Shao ()
Additional contact information
Carine Z. J. Lim: National University of Singapore
Yan Zhang: National University of Singapore
Yu Chen: Agency for Science, Technology and Research
Haitao Zhao: National University of Singapore
Mary C. Stephenson: National University of Singapore
Nicholas R. Y. Ho: National University of Singapore
Yuan Chen: National University of Singapore
Jaehoon Chung: Agency for Science, Technology and Research
Anthonin Reilhac: National University of Singapore
Tze Ping Loh: National University of Singapore
Christopher L. H. Chen: National University Hospital
Huilin Shao: National University of Singapore

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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 β (Aβ) 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 Aβ aggregates preferentially bind with exosomes. We thus define a population of Aβ as exosome-bound (Aβ42+ CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating Aβ, the exosome-bound Aβ measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.

Date: 2019
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DOI: 10.1038/s41467-019-09030-2

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