Glycopeptide Nanofiber Platform for Aβ-Sialic Acid Interaction Analysis and Highly Sensitive Detection of Aβ

Abstract

The variation of amyloid β peptide (Aβ) concentration and Aβ aggregation are closely associated with the etiology of Alzheimer’s diseases (AD). The interaction of Aβ with the monosialoganglioside-rich neuronal cell membrane has been suggested to influence Aβ aggregation. Therefore, studies on the mechanism of Aβ and sialic acids (SA) interaction would greatly contribute to better understanding the pathogenesis of AD. Herein, we report a novel approach for Aβ–SA interaction analysis and highly sensitive Aβ detection by mimicing the cell surface presentation of SA clusters through engineering of SA-modified peptide nanofiber (SANF). The SANF displayed well-ordered 1D nanostructure with high density of SA on surface. Using FAM-labeled Aβ fragments of Aβ1–16, Aβ16–23, and Aβ24–40, the interaction between Aβ and SA was evaluated by the fluorescence titration experiments. It was found that the order of the SA-binding affinity was Aβ1–16 > Aβ24–40 > Aβ16–23. Importantly, the presence of full-length Aβ1–40 monomer triggered a significant fluorescence enhancement due to the multivalent binding of Aβ1–40 to the nanofiber. This fluorescent turn-on response showed high selectivity and sensitivity for Aβ1–40 detection and the method was further used for Aβ aggregation process monitoring and inhibitor screening. The results suggest the proposed strategy is promising to serve as a tool for mechanism study and the early diagnosis of Alzheimer’s disease.

Rod-like amphiphilic AIE-active NIR probe enables super-early precise in-vivo detection of Aβ fibrils/plaques

“…It has been speculated that the reason for the failure of early drug intervention on AD is probably that intervention in the phase is not early enough, which in turn is greatly related to the e cient capture of biological manifestations rather than clinical manifestations in the early diagnosis 47,48 . The experimental results obtained with AIE-CNPy-AD is of great signi cance because APP/PS1 transgenic mice are found to exhibit memory de cits from 5 months old on which is early clinical presentations, con rming that AIE-CNPy-AD can diagnose AD of APP/PS1 transgenic mice during the period of early biological manifestations, prior to the appearance of clinical presentations 43,47,49 . Furthermore, as shown in Fig.…”

Rationally Designing Simple Rod-Like Amphiphilic NIR-Emissive AIE Probes for Precise In-Vivo Detection of Aβ Fibrils/Plaques at A Super-Early Stage

“…4748 The experimental results obtained with AIE-CNPy-AD is of great significance because APP/PS1 transgenic mice are found to exhibit memory deficits from 5 months old on which is early clinical presentations, confirming that AIE-CNPy-AD can diagnose AD of APP/PS1 transgenic mice during the period of early biological manifestations, prior to the appearance of clinical presentations. 43,47,49 Furthermore, as shown in Figure S15, ThS could neither give discriminatory signals between the APP/PS1 transgenic mice and wild-type mice nor provide distinct signals among mice of different ages, manifesting that our probe outperforms the clinically used gold-standard probe and could be used as an upgraded alternative to the commercially available ones.…”

Rationally Designing Simple Rod-Like Amphiphilic NIR-Emissive AIE Probes for Precise In-Vivo Detection of Aβ Fibrils/Plaques at A Super-Early Stage

“…4748 The experimental results obtained with AIE-CNPy-AD is of great significance because APP/PS1 transgenic mice are found to exhibit memory deficits from 5 months old on which is early clinical presentations, confirming that AIE-CNPy-AD can diagnose AD of APP/PS1 transgenic mice during the period of early biological manifestations, prior to the appearance of clinical presentations. 43,47,49 Furthermore, as shown in Figure S15 Figure 6A, 6F, and Figure S16, the Aβ plaques were imaged with high resolution and high contrast. Moreover, it can be clearly observed that the Aβ plaques in brain slices of 6-month-old APP/PS1 transgenic mice were larger and richer in number than those of 4-month-old APP/PS1 transgenic mic, while no significant Aβ plaques were found in the brain slices of 2-month-old, 3-month-old APP/PS1 transgenic mice ( Figure S16), and all the age-matched WT mice ( Figure S17).…”