Light-Up Nonthiolated Aptasensor for Low-Mass, Soluble Amyloid-β₄₀ Oligomers at High Salt Concentrations

Herein, a light-up nonthiolated aptasensor was developed for low-mass, soluble amyloid-β₄₀ oligomers (LS-Aβ_40-O). Au nanoparticles (AuNP) were employed as colorimetric probes, and the nonthiolated aptamers (Apt) were adsorbed on AuNP surfaces, acting as binding elements for LS-Aβ_40-O. The aggregation of AuNPs was induced when Apt-modified AuNPs (Apt@AuNPs) were under high-salt conditions. However, upon the addition of LS-Aβ_40-O into the Apt@AuNP solution, the salt tolerance of the AuNPs was greatly enhanced. Further studies confirmed that the formed LS-Aβ_40-O-Apt complex attached onto the AuNP surfaces via interactions between LS-Aβ_40-O and Au, which led to electrostatic and steric stabilization of the AuNPs under high-salt conditions. On the basis of this outcome, a sensitive light-up nonthiolated aptasensor for LS-Aβ_40-O was achieved with a detection limit of 10.0 nM and a linear range from 35.0 to 700 nM in a 175 mM NaCl solution. Cerebrospinal-fluid (CSF) samples from healthy persons and Alzheimer's disease (AD) patients were successfully distinguished by using this proposed method. The concentrations of LS-Aβ_40-O in the CSF of AD patients were of nanomolar grade, but there was no detectable LS-Aβ_40-O in those of the healthy persons. This work provides a new insight into the interaction between Apt@AuNPs and Aβ_40-O and also develops a simple, rapid, highly selective and sensitive, and applicable method for LS-Aβ_40-O detection in real CSF samples, which is significant for the diagnosis of AD.