Subtyping of circulating exosome-bound amyloid β reflects brain plaque deposition
Open accessAbstract
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.
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Lim et al. developed the Amplified Plasmonic Exosome (APEX) platform for multiplexed analysis of exosome populations directly from blood samples of patients with Alzheimer's disease.
“Lim et al. have developed a highly sensitive analytical platform, termed Amplified Plasmonic Exosome (APEX), designed for multiplexed analysis of exosome populations directly from the blood samples of patients with AD [232].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [232]
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- Authors
- Lim, C. Z. J., Zhang, Y., Chen, Y., Zhao, H., Stephenson, M. C., Ho, N. R. Y., Chen, Y., Chung, J., Reilhac, A., Loh, T. P., Chen, C. L. H., & Shao, H.
- Affiliations
- National University of Singapore (SG)
- Agency for Science, Technology and Research (SG)
- Corresponding author
- Shao, Huilin
- ORCID
- Venue
- Nature Communications
- Published
- 2019-03-08
- Volume
- 10
- Issue
- 1
- Pages
- 1144-1144
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6408581
- OpenAlex
- W2922092934
- Cited by
- 209
- References
- 10
- Citations by year
- 2026: 19 · 2025: 31 · 2024: 34 · 2023: 24 · 2022: 28 · 2021: 37 · 2020: 24 · 2019: 12
- FWCI
- 17.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Education, India
- National Medical Research Council
- Institute of Molecular and Cell Biology
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, exosomes, blood biomarkers, plasmonic nanostructures, amyloid plaques, CD63, positron emission tomography, liquid biopsy
- MeSH terms
- THP-1 Cells, Alzheimer Disease, Brain, Humans, Neurons, Peptide Fragments, Serum Albumin, Bovine, Biosensing Techniques, Case-Control Studies, Amyloid beta-Peptides, Surface Plasmon Resonance, Cell Line, Tumor, Microfluidic Analytical Techniques, Positron-Emission Tomography, Exosomes, Plaque, Amyloid, Tetraspanin 30, Human Umbilical Vein Endothelial Cells, Protein Aggregates
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