Abstract
Precise and early detection of β-amyloid (Aβ) deposits in situ and in real time is pivotal to the diagnosis and early intervention of Alzheimer’s disease (AD). Optical imaging stands out to be a promising technique for such a task; however, it still remains a big challenge, due to the lack of high-performance imaging contrast agent. Restricted by poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, as well as the aggregation-caused quenching effect, the widely used gold-standard probes cannot be used for early in-vivo imaging of Aβ deposits. Herein, we integrate the Aβ deposits-favored geometry, amphiphilic and zwitterionic molecular structure, extended D-π-A electronic structure, and 3D conformation into one molecule, facilely establishing a simple and economic imaging contrast agent that enjoys high specificity and affinity to Aβ deposits, good BBB penetrability, bright red/near-infrared fluorescence, low interference from autofluorescence, aggregation-induced emission (AIE) feature, high signal-to-noise ratio (SNR), and high contrast. In-vitro, ex-vivo, and in-vivo experiments with different strains of mice indicate that AIE-CNPy-AD holds the universality to Aβ deposits identification. Noteworthily, AIE-CNPy-AD is even able to precisely trace the small and sparsely-distributed Aβ deposits in AD model mice as young as 4-month-old APP/PS1 mice, the youngest having Aβ deposits. Moreover, the present probe could clearly reveal the increase and enlargement of Aβ deposits as the mice grow. Therefore, AIE-CNPy-AD might be an ideal alternative for early AD diagnosis and highly reliable monitoring of AD progression.
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Acknowledgements
This work was supported by the National Natural Sciences Foundation of China (21788102, 21875064, 81903545, 21604023, 21790361), Shanghai Science and Technology Commission Basic Project-Shanghai Natural Science Foundation (21ZR1417600), Shanghai Municipal Science and Technology Major Project (2018SHZDZX03), Programme of Introducing Talents of Discipline to Universities (B16017), Shanghai Science and Technology Committee (17520750100), Beijing New-Star Plan of Science and Technology (Z201100006820009), Shanghai Sailing Program (16YF1402200), and the Fundamental Research Funds for the Central Universities.
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Wang, Y., Mei, D., Zhang, X. et al. Visualizing Aβ deposits in live young AD model mice with a simple red/near-infrared-fluorescent AIEgen. Sci. China Chem. 65, 339–352 (2022). https://doi.org/10.1007/s11426-021-1113-0
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DOI: https://doi.org/10.1007/s11426-021-1113-0