Simultaneous Monitoring of Amyloid-β (Aβ) Oligomers and Fibrils for Effectively Evaluating the Dynamic Process of Aβ Aggregation

Herein, we provide a proof of concept for a novel strategy that targets the assessment of the aggregation of amyloid-beta (A beta) by simultaneously determining its oligomers (A beta o) and fibrils (A beta f) in one analytical system. By fabricating and combining two immunosensors for A beta o and A beta f, respectively, we constructed a two-channel electrochemical system. The ratio of A beta f to A beta o was calculated and taken as a possible criterion for evaluating the extent of aggregation. Thereby, the presence of and transformation between oligomers and fibrils were accurately probed by incubating the A beta monomer for different times and then calculating the ratios of A beta f to A beta o. The applicability of this method was further validated by tracking the dynamic progress of A beta aggregation in the cerebrospinal fluid and tissues of Alzheimer's disease (AD) rats, which revealed that the ratio of A beta f to A beta o in rat brain gradually increased with the progression of AD, which was indicative of the severity of peptide aggregation during this process. Overall, this study represents the first example of a quantitative strategy for precisely evaluating the aggregation process that is related to pathological events in AD brain.