Real-Time Detection and Visualization of Amyloid-β Aggregates Induced by Hydrogen Peroxide in Cell and Mouse Models of Alzheimer’s Disease

Xueli Wang, Ashok Iyaswamy, Di Xu, Senthilkumar Krishnamoorthi, Sravan Gopalkrishnashetty Sreenivasmurthy, Yuncong Yang, Yinhui Li, Chen Chen, Min Li, Hung-Wing Li*, Man Shing Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Oxidative stress, caused by an imbalance between the production and the accumulation of reactive oxygen species (ROS), is a prominent cause of the neurotoxicity induced by aggregated amyloid-β (Aβ) in Alzheimer’s disease (AD). Tools that can directly detect and monitor the presence and amount of Aβ-induced ROS are still lacking. We report herein the first Aβ-targeted ratiometric H2O2-responsive fluorescent probe for real-time detection and monitoring of the Aβ-induced H2O2 level in cell and AD mouse models. The H2O2-responsive probe is constructed based on a methylamino-substituted quinolinium-based cyanine as the fluorescence moiety and a phenylboronate ester as the sensing reaction site. This sensing probe exhibits a large emission wavelength shift of ∼87 nm upon reacting with H2O2, a high binding selectivity for Aβ, and a faster response toward H2O2 in the presence of Aβ, concomitant with an enhanced fluorescence intensity, hence greatly boosting the sensitivity of in-situ H2O2 detection. This biocompatible and nontoxic probe is capable of ratiometrically detecting and imaging endogenous H2O2 induced by Aβ in a neuronal cell model. Remarkably, this Aβ-targeted H2O2-responsive probe is also able to detect, monitor, and differentiate different Aβ-induced H2O2 levels in real time in different age groups of transgenic AD mice in which the cerebral H2O2 level increases age dependently concomitant with the plaque contents. Therefore, this smart probe can act as a powerful tool to diagnose high-risk subjects and diseased brains of AD and to further study the role of ROS in AD pathology.
Original languageEnglish
Number of pages9
JournalACS applied materials & interfaces
DOIs
Publication statusE-pub ahead of print - 22 Jul 2022

Scopus Subject Areas

  • Materials Science(all)

User-Defined Keywords

  • Alzheimer’s disease
  • Aβ-enhanced sensitivity
  • Aβ-targeting
  • H2O2-responsive fluorescent probe
  • in-vivo detection
  • ratiometric imaging
  • Alzheimer's disease

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