Abstract

One of the pathological hallmarks of Alzheimer’s disease (AD) is the abnormal aggregation of amyloid beta (Aβ) peptides. Therefore the detection of Aβ peptides and imaging of amyloid plaques are considered as promising diagnostic methods for AD. Here we report a bifunctional nanoprobe prepared by conjugating gold nanoparticles (AuNPs) with Rose Bengal (RB) dye. RB is chosen due to its unique Raman fingerprints and affinity with Aβ peptides. After the conjugation, Raman signals of RB were significantly enhanced due to the surface-enhanced Raman scattering (SERS) effect. Upon binding with Aβ42 peptides, a spectrum change was detected, and the magnitude of the spectrum changes can be correlated with the concentration of target peptides. The peptide/probe interaction also induced a remarkable enhancement in the probes’ fluorescence emission. This fluorescence enhancement was further utilized to image amyloid plaques in the brain slices from transgenic mice. In this study, the RB-AuNPs were used for both SERS-based detection of Aβ42 peptides and fluorescence-based imaging of amyloid plaques. Compared to monofunctional probes, the multifunctional probe is capable to provide more comprehensive pathophysiological information, and therefore, the implementation of such multifunctional amyloid probes is expected to help the investigation of amyloid aggregation and the early diagnosis of AD.

Highlights

  • Neurodegenerative disorders are diseases caused by the death of neurons and malfunction of the neural circuit

  • One reason is that fluorescence imaging is an intuitive method and can achieve real-time image acquisition, which makes it an ideal complementary imaging modality for Raman imaging. Another advantage of F-Surface-enhanced Raman scattering (SERS) probes is that many fluorescent dyes such as fluorescein isothiocyanate (FITC)[20] and Rhodamine B derivatives[24] can be readily used as Raman reporters when they are conjugated with nanostructures, which makes the preparation of fluorescent SERS (F-SERS) probes much facile

  • The results show that the changes in the ratio of major peaks are associated with amyloid peptides. (Supplementary Fig. S5) It is interesting to see that the changes of Rpeak value are detectable even in mouse brain slices that were stained with Rose Bengal (RB)-a bifunctional gold nanoparticles (AuNPs) (Supplementary Fig. S6), suggesting a potential amyloid mapping strategy based on Rpeak values

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Summary

Introduction

Neurodegenerative disorders are diseases caused by the death of neurons and malfunction of the neural circuit. To overcome the aforementioned limitations, an indirect-SERS strategy has been proposed: instead of interrogating the Raman signals from the proteins, an additional Raman reporter with large Raman cross-section can be attached to the nanostructures and the reporter is allowed to react with the target protein in order to generate detectable changes in the Raman spectra[15,16] This type of SERS probes has been successfully applied to detect DNA, protein and other bio-molecules[17]. Another advantage of F-SERS probes is that many fluorescent dyes such as fluorescein isothiocyanate (FITC)[20] and Rhodamine B derivatives[24] can be readily used as Raman reporters when they are conjugated with nanostructures, which makes the preparation of F-SERS probes much facile In this presented work, we report a bifunctional gold nanoparticles (AuNPs) for SERS based detection of Aβ42 peptides and fluorescence imaging of amyloid plaques. These results suggest that the conjugated RB-AuNPs can be used as a bifunctional probe for amyloid detection, and as a diagnostic tool for the onset of AD

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