Development of DNA Aptamer as a β-Amyloid Aggregation Inhibitor

Developing a strategy of modulating β-amyloid (Aβ) aggregation with low cost, easy synthesis, high efficiency, and biosafety is significant and a challenge for Alzheimer's disease (AD) therapy. Herein, DNA aptamer (Aβ-Apt) against Aβ₄₂ obtained by in vitro selection was developed as a potent inhibitor of Aβ₄₂ aggregation for the first time. Indeed, the Aβ₄₂ monomer fibrillation was inhibited completely by Aβ-Apt. Notably, the inhibition effect of Aβ-Apt on the Aβ₄₂ oligomer aggregation was more obvious than that on the Aβ₄₂ monomer aggregation. It was presumed that the distinguishing effect may be attributed to different binding behaviors of Aβ-Apt with Aβ₄₂ monomer and Aβ₄₂ oligomer. Surface plasmon resonance analysis demonstrated that Aβ-Apt specifically recognized Aβ₄₂ monomer and Aβ₄₂ oligomer. Furthermore, the binding affinity of Aβ-Apt with Aβ₄₂ oligomer was larger than that of Aβ-Apt with Aβ₄₂ monomer. This work provided a promising platform with high efficiency for manipulating Aβ aggregation.