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.

Detecting Alzheimer’s disease from blood samples is challenging because amyloid β blood levels are lower than the ELISA detection limit. Here the authors capture amyloid β bound to circulating exosomes on a plasmonic nanosensor, followed by enzymatic amplification to improve detection sensitivity.

Details

Title
Subtyping of circulating exosome-bound amyloid β reflects brain plaque deposition
Author
Lim Carine Z J 1 ; Zhang, Yan 1 ; Chen, Yu 2 ; Zhao, Haitao 1   VIAFID ORCID Logo  ; Stephenson, Mary C 3 ; Ho Nicholas R Y 4   VIAFID ORCID Logo  ; Chen, Yuan 1 ; Chung, Jaehoon 2 ; Anthonin, Reilhac 3 ; Loh, Tze Ping 5 ; Chen Christopher L H 6 ; Shao Huilin 7 

 National University of Singapore, Department of Biomedical Engineering, Faculty of Engineering, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National University of Singapore, Biomedical Institute for Global Health Research and Technology, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
 Agency for Science, Technology and Research, Institute of Microelectronics, Singapore, Singapore (GRID:grid.185448.4) (ISNI:0000 0004 0637 0221) 
 National University of Singapore, Clinical Imaging Research Center, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
 National University of Singapore, Biomedical Institute for Global Health Research and Technology, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); Agency for Science, Technology and Research, Institute of Molecular and Cell Biology, Singapore, Singapore (GRID:grid.185448.4) (ISNI:0000 0004 0637 0221) 
 National University of Singapore, Biomedical Institute for Global Health Research and Technology, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National University Hospital, Department of Laboratory Medicine, Singapore, Singapore (GRID:grid.412106.0) (ISNI:0000 0004 0621 9599) 
 National University Hospital, Memory Ageing and Cognition Center, Singapore, Singapore (GRID:grid.412106.0) (ISNI:0000 0004 0621 9599); National University of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
 National University of Singapore, Department of Biomedical Engineering, Faculty of Engineering, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National University of Singapore, Biomedical Institute for Global Health Research and Technology, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); Agency for Science, Technology and Research, Institute of Molecular and Cell Biology, Singapore, Singapore (GRID:grid.185448.4) (ISNI:0000 0004 0637 0221); National University of Singapore, Department of Surgery, Yong Loo Lin School of Medicine, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2188969989
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.