Selective amyloid β oligomer assay based on abasic site-containing molecular beacon and enzyme-free amplification

Amyloid-beta (A beta) oligomers are highly toxic species in the process of A beta aggregation and are regarded as potent therapeutic targets and diagnostic markers for Alzheimer's disease (AD). Herein, a label-free molecular beacon (MB) system integrated with enzyme-free amplification strategy was developed for simple and highly selective assay of A beta oligomers. The MB system was constructed with abasic site (A beta site)-containing stem-loop DNA and a fluorescent ligand 2-amino-5,6,7-trimethyl-1,8-naphyridine (ATMND), of which the fluorescence was quenched upon binding to the A beta site in DNA stem. Enzyme free amplification was realized by target-triggered continuous opening of two delicately designed MBs (MB1 and MB2). Target DNA hybridization with MB1 and then MB2 resulted in the release of two ATMND molecules in one binding event. Subsequent target recycling could greatly amplify the detection sensitivity due to the greatly enhanced turn-on emission of ATMND fluorescence. Combining with A beta oligomers aptamers, the strategy was applied to analyze A beta oligomers and the results showed that it could quantify A beta oligomers with high selectivity and monitor the A beta aggregation process. This novel method may be conducive to improve the diagnosis and pathogenic study of Alzheimer's disease. (C) 2015 Elsevier B.V. All rights reserved.