Cited by 123Alzheimer's disease research and treatmentsMolecular Sensors and Ion DetectionLuminescence and Fluorescent Materials

Turn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo

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Yang, Jing, Yin, Wei, Van, Richard, Yin, Keyi, Wang, Peng, Zheng, Chao, Zhu, Biyue, Ran, Kathleen +4 more·2020·Nature Communications

Published version of a preprint

Abstract

Turn-on fluorescence imaging is routinely studied; however, turn-on chemiluminescence has been rarely explored for in vivo imaging. Herein, we report the design and validation of chemiluminescence probe ADLumin-1 as a turn-on probe for amyloid beta (Aβ) species. Two-photon imaging indicates that ADLumin-1 can efficiently cross the blood–brain barrier and provides excellent contrast for Aβ plaques and cerebral amyloid angiopathy. In vivo brain imaging shows that the chemiluminescence signal of ADLumin-1 from 5-month-old transgenic 5xFAD mice is 1.80-fold higher than that from the age-matched wild-type mice. Moreover, we demonstrate that it is feasible to further d ually- a mplify s ignal via c hemiluminescence r esonance e nergy t ransfer (DAS-CRET) using two non-conjugated smart probes (ADLumin-1 and CRANAD-3) in solutions, brain homogenates, and in vivo whole brain imaging. Our results show that DAS-CRET can provide a 2.25-fold margin between 5-month-old 5xFAD mice and wild type mice. We believe that our strategy could be extended to other aggregating-prone proteins.

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  • Cinnamic derivatives can cross the blood-brain barrier and insert into the beta sheet of amyloid β proteins.

    “Cinnamic derivatives can cross the BBB and insert into the beta sheet of amyloid β proteins41.”

    From Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system (2025) · cites this paper as [41]

    The Results (In vivo imaging with ADLumin-1; page unavailable) report that ADLumin-1 crossed the blood–brain barrier in mice. The Results (Design and synthesis of ADLumin-1; page unavailable) say its binding moiety has the potential to insert into Aβ beta sheets, but the paper does not identify the probes as cinnamic derivatives or establish insertion as a demonstrated fact. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Yang, J., Yin, W., Van, R., Yin, K., Wang, P., Zheng, C., Zhu, B., Ran, K., Zhang, C., Kumar, M., Shao, Y., & Ran, C.
Affiliations
  • Harvard University (US)
  • University of Oklahoma (US)
  • Massachusetts Institute of Technology (US)
Corresponding author
Ran, Chongzhao
Venue
Nature Communications
Published
2020-08-13
Volume
11
Issue
1
Pages
4052-4052
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3048903908
Cited by
123
References
73
Citations by year
2026: 16 · 2025: 16 · 2024: 24 · 2023: 24 · 2022: 13 · 2021: 27 · 2020: 3
FWCI
10.07
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • ChemRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by-nc-nd)
Funders
U.S. Department of Health & Human Services | NIH | National Institute on Aging (R21AG059134, R01AG055413)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
  • Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
Keywords
chemiluminescence probe, amyloid-beta detection, chemiluminescence resonance energy transfer, two-photon imaging, blood-brain barrier penetration, cerebral amyloid angiopathy, amyloid plaques, 5xFAD mice, in vivo brain imaging
MeSH terms
Animals, Luminescent Measurements, Amyloid beta-Peptides, Luminescence, Mice, Molecular Imaging, Optical Imaging, Protein Aggregates

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