Abstract
Purpose
Selective visualization of amyloid-β and tau protein deposits will help to understand the pathophysiology of Alzheimer’s disease (AD). Here, we introduce a novel fluorescent probe that can distinguish between these two deposits by multispectral fluorescence imaging technique.
Procedures
Fluorescence spectral analysis was performed using AD brain sections stained with novel fluorescence compounds. Competitive binding assay using [3H]-PiB was performed to evaluate the binding affinity of BF-188 for synthetic amyloid-β (Aβ) and tau fibrils.
Results
In AD brain sections, BF-188 clearly stained Aβ and tau protein deposits with different fluorescence spectra. In vitro binding assays indicated that BF-188 bound to both amyloid-β and tau fibrils with high affinity (K i < 10 nM). In addition, BF-188 showed an excellent blood–brain barrier permeability in mice.
Conclusion
Multispectral imaging with BF-188 could potentially be used for selective in vivo imaging of tau deposits as well as amyloid-β in the brain.
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Acknowledgment
This study was supported by the research fund from Sumitomo Electric Industries Ltd, the Small Business Innovation Research (SBIR) program of Japan, and the Grant-in-Aid for Scientific Research on Priority Areas “Integrative Brain Research” from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (20019006), and Japan Society for the Promotion of Science (JSPS).
Conflict of Interest
The authors declare no competing financial interests.
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Harada, R., Okamura, N., Furumoto, S. et al. Use of a Benzimidazole Derivative BF-188 in Fluorescence Multispectral Imaging for Selective Visualization of Tau Protein Fibrils in the Alzheimer’s Disease Brain. Mol Imaging Biol 16, 19–27 (2014). https://doi.org/10.1007/s11307-013-0667-2
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DOI: https://doi.org/10.1007/s11307-013-0667-2