RNA aptamers selected against amyloid β-peptide (Aβ) inhibit the aggregation of Aβ

Aggregation of amyloid beta-peptide (A beta) is closely related to the pathogenesis of Alzheimer's disease (AD). Much effort has been devoted to the construction of molecules that suppress and neutralize the toxicity of A beta. Using a systematic evolution of ligands using the exponential enrichment (SELEX) procedure, we have constructed RNA aptamers that bind to A beta 1-40 and inhibit aggregation. To obtain the RNA aptamers, we applied an oligomer model of A beta as a selection target using A beta 1-40 conjugated with a colloidal gold nanoparticle (A beta-AuNP). Although the selected RNA sequences did not converge, two RNA aptamers (N2 and E2) bound more tightly to A beta-AuNP than the other aptamers. The dissociation constants (K-d) of N2-Flu and E2-Flu, fluorescent-labeled RNAs, to monomeric A beta 1-40 peptide were estimated as K-d = 21.6 and 10.9 mu M, respectively. ELISA revealed that these aptamers can inhibit Ab aggregation efficiently. Transmission electron micrographs indicated that N2 and E2 aptamers can stop the fibrillization of A beta 1-40. The selected RNA aptamers may have potential as therapeutic agents for AD pathogenesis.