High-fidelity imaging of amyloid-beta deposits with an ultrasensitive fluorescent probe facilitates the early diagnosis and treatment of Alzheimer's Disease
Rongrong Tao, Ning Wang, Tianruo Shen, Yuhang Tan, Yong Ren, Wenjing Wei, Mei‐Hua Liao, Davin Tan, Chunzhi Tang, Nenggui Xu, Huan Wang, Xiaogang Liu, Xin Li
Abstract
Background: Imaging amyloid-beta (A) 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 A deposits, and exhibited ca 10-fold less background fluorescence and 5-10 folds of improved signal-to-background contrast upon binding A deposits. These desirable features endowed AH-2 the sensitivity to detect A deposition in naturally aging wild-type mice.