A turn-on unlabeled colorimetric biosensor based on aptamer-AuNPs conjugates for amyloid-β oligomer detection

Amyloid-β oligomers (AβO) have been identified as core biomarkers for early diagnosis of Alzheimer's disease (AD). For the first time, a "turn-on" unlabeled colorimetric aptasensor based on aptamer-polythymine (polyT)-polyadenine (polyA)-gold nanoparticles (pA-pT-apt@AuNPs) was developed for highly sensitive and specific detection of amyloid-β_1-40 oligomers (Aβ40-O). In this system, polyA sequence could preferentially anchor onto AuNPs surface as well as reduce the non-specific adsorption, and the aptamer could form upright conformation for the specific recognition of Aβ40-O. The aggregation of pA-pT-apt@AuNPs was induced by MgCl₂. However, the addition of Aβ40-O enabled the aptamer fold adaptively upon recognition and aptamer-Aβ40-O complex formed surrounding AuNPs, effectively stabilizing pA-pT-apt@AuNPs against salt-induced aggregation, therefore the color of pA-pT-apt@AuNPs solution still retained red. Based on this principle, the proposed aptasensor exhibited high sensitivity with the limit of detection of 3.03 nM and a linear detectable range from 10.00 nM to 100.0 nM. The superb sensitivity was achieved via the optimization of the length of polyA and polyT spacer. This pA-pT-apt@AuNPs based colorimetric aptasensor provides a rapid, cost-effective, highly sensitive detection method for Aβ40-O, which is valuable for the early diagnosis of AD.