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Theranostics 2022; 12(6):2549-2559. doi:10.7150/thno.68743 This issue Cite

Research Paper

High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer's Disease

Rongrong Tao1, Ning Wang2, Tianruo Shen3, Yuhang Tan1, Yong Ren2, Wenjing Wei1, Meihua Liao1, Davin Tan3, Chunzhi Tang1, Nenggui Xu1, Huan Wang4✉, Xiaogang Liu3✉, Xin Li2✉

1. Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China
2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 301158, China
3. Fluorescence Research Group, Singapore University of Technology and Design, 8 Somapah Road, Singapore 487372, Singapore
4. College of Life Science and Technology, Dalian University, Dalian, Liaoning 116622, China

✉ Corresponding authors: lixin81edu.cn, xiaogang_liuedu.sg or 0012669edu.cn

Citation:
Tao R, Wang N, Shen T, Tan Y, Ren Y, Wei W, Liao M, Tan D, Tang C, Xu N, Wang H, Liu X, Li X. High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer's Disease. Theranostics 2022; 12(6):2549-2559. doi:10.7150/thno.68743. https://www.thno.org/v12p2549.htm
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Abstract

Graphic abstract

Background: Imaging amyloid-beta (Aβ) deposits with high fidelity in naturally aging brains is crucial for the early diagnosis of Alzheimer's disease (AD). However, this is impeded by the lack of highly sensitive probes.

Methods: By conducting computational modelling to quantitatively fine-tune the twisted intramolecular charge transfer (TICT) tendency of Thioflavin T (ThT) analogues, we developed an ultrasensitive probe AH-2. AH-2 retained the binding affinity and binding mode of ThT towards Aβ deposits, and exhibited ca 10-fold less background fluorescence and 5-10 folds of improved signal-to-background contrast upon binding Aβ deposits. These desirable features endowed AH-2 the sensitivity to detect Aβ deposition in naturally aging wild-type mice.

Results: AH-2 imaging revealed that Aβ puncta signals appeared near the nuclei in young mice and spread through the intracellular and extracellular compartments in older mice. Moreover, Aβ deposits were observed to emerge earlier in mice cerebral cortex than in the hippocampus region. Given this desirable sensitivity and good spatiotemporal resolution, AH-2 was successfully applied in the preclinical evaluation of Aβ-targeted treatment by melatonin.

Conclusions: We expect that AH-2 is promising for early diagnosis of AD and will serve as a sensitive tool for studying Aβ-related AD pathology.

Keywords: fluorescent probe, fluorescent imaging, amyloid-beta, Alzheimer's disease, intramolecular charge transfer

Citation styles

APA
Tao, R., Wang, N., Shen, T., Tan, Y., Ren, Y., Wei, W., Liao, M., Tan, D., Tang, C., Xu, N., Wang, H., Liu, X., Li, X. (2022). High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer's Disease. Theranostics, 12(6), 2549-2559. https://doi.org/10.7150/thno.68743.

ACS
Tao, R.; Wang, N.; Shen, T.; Tan, Y.; Ren, Y.; Wei, W.; Liao, M.; Tan, D.; Tang, C.; Xu, N.; Wang, H.; Liu, X.; Li, X. High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer's Disease. Theranostics 2022, 12 (6), 2549-2559. DOI: 10.7150/thno.68743.

NLM
Tao R, Wang N, Shen T, Tan Y, Ren Y, Wei W, Liao M, Tan D, Tang C, Xu N, Wang H, Liu X, Li X. High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer's Disease. Theranostics 2022; 12(6):2549-2559. doi:10.7150/thno.68743. https://www.thno.org/v12p2549.htm

CSE
Tao R, Wang N, Shen T, Tan Y, Ren Y, Wei W, Liao M, Tan D, Tang C, Xu N, Wang H, Liu X, Li X. 2022. High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer's Disease. Theranostics. 12(6):2549-2559.

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