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Reporting amyloid beta levels via bioluminescence imaging with amyloid reservoirs
Author(s) -
Yang Jing,
Ding Weihua,
Zhu Biyue,
Shen Shiqian,
Ran Chongzhao
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.054652
Subject(s) - bioluminescence imaging , luciferase , bioluminescence , in vivo , preclinical imaging , amyloid (mycology) , chemistry , genetically modified mouse , biophysics , pathology , transgene , biology , medicine , biochemistry , transfection , microbiology and biotechnology , gene
Background Bioluminescence imaging has changed daily practice in preclinical research of cancers and other diseases in the last decades; however, it has been rarely applied in preclinical research of Alzheimer’s disease (AD). Method In this report, we demonstrated that bioluminescence imaging could be used to report the levels of amyloid beta (Ab) species in vivo. We hypothesized that AkaLumine, a newly discovered substrate for luciferase, could bind to Ab aggregates and plaques. We further speculated that the Ab species have the reservoir capacity to sequester and release AkaLumine to control the bioluminescence intensity, which could be used to report the levels of Abs. Results Our hypotheses have been validated via in vitro tests, mimic phantom imaging, and in vivo imaging using transgenic AD mice that were virally transduced with aka Luciferase (AkaLuc), a new luciferase that generates bioluminescence in the near infrared window. As expected, compared to the control group, we observed that the Ab group showed lower bioluminescence intensity due to AkaLumine sequestering at early time points, while higher intensity due to AkaLumine releasing at later time points. Lastly, we demonstrated that this method could be used to monitor AD progression and therapeutic effectiveness of avagacestat, a well‐studied gamma‐secretase inhibitor. Conclusion Our approach can be easily implanted into daily imaging experiments. We believe that our method has tremendous potential to change daily practice of preclinical AD research.