Amyloid β-peptide oligomer (AβO) has received extensive attention from researchers because of its clinical therapeutic intervention targets and the value of reliable biological macromolecules markers for early diagnosis of Alzheimer's disease. We have developed a novel label-free electrochemical detection sensor for AβO based on hybridization chain reaction (HCR)-triggered poly adenine to absorb silver nanoparticles (AgNPs). In this method, we first use the "capture probe" to immobilize the aptamer 1 on the surface of the gold electrode (GE) via poly adenine-Au. Next, aptamer 2 and AβO were deposited on the electrode surface. The HCR process was initiated by the aptamer 2 fragment as a primer, producing a large number of long DNA sequences, which contained many adenines. Thereafter, the HCR product with long-repeated adenines could absorb many AgNPs on the surface of the electrode, which were used for subsequent electrochemical stripping of the AgNPs. The concentration range of the electrochemical signal of AβO was 1 pM–10 nM, and the detection limit was 430 fM, which indicated that that the detection system has high selectivity for the target protein. A versatile label-free electrochemical platform for detecting amyloid β-peptide oligomers via proximity hybridization-triggered DNA assembly was developed. [Display omitted] • A label-free electrochemical sensor for amyloid β oligomers detection based on HCR triggered poly adenine to absorb silver nanoparticles. • The signal amplification is based on HCR and electrochemical stripping signal of the AgNPs. • The biosensor can detect amyloid β oligomers down to 430 fM level with a dynamic range spanning 4 orders of magnitude. [ABSTRACT FROM AUTHOR]