A ZIF-8-modified electrochemical biosensor for sensitive Aβ aggregation monitoring and Alzheimer's disease drug screening

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RSC Adv., 2026, 16,20855-20865DOI: 10.1039/D6RA00907G, Paper Open Access &nbsp This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.Shang-Chi Chien, Yin-Chen Chien, Hung-Ju Wang, Jung-Chih ChenThe aggregation state …

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A ZIF-8-modified electrochemical biosensor for sensitive Aβ aggregation monitoring and Alzheimer's disease drug screening

* Corresponding authors

a Department of Electronics and Electrical Engineering, National Yang Ming Chiao Tung University, Hsinchu City 300, Taiwan
E-mail: [email protected]

b Institute of Intelligent Bioelectrical Engineering, National Yang Ming Chiao Tung University, Hsinchu City 300, Taiwan

c College of Artificial Intelligence, National Yang Ming Chiao Tung University, Hsinchu City 300, Taiwan

d Catholic Mercy Hospital, Catholic Mercy Medical Foundation, Hsinchu County 303, Zhubei City, Taiwan

e Medical Device Innovation & Translation Center, National Yang Ming Chiao Tung University, Taipei City 112, Taiwan

Abstract

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder driven by the abnormal aggregation of β-amyloid (Aβ) into oligomers, fibrils, and plaques. Current therapeutic strategies primarily alleviate symptoms but struggle to prevent aggregation due to the dynamic nature of Aβ species and prolonged drug development cycles. Sensitive and real-time monitoring of Aβ structural transitions is therefore essential for understanding disease progression and evaluating potential inhibitors. In this study, we developed a ZIF-8-modified electrochemical biosensor capable of translating Aβ42 conformational changes into quantifiable current signals, providing a promising platform for monitoring dynamic aggregation. The aggregation behavior of Aβ42 was systematically characterized using dynamic light scattering (DLS), electrochemical measurements, and Thioflavin T (ThT) fluorescence combined with ultrafiltration. A critical transition from the lag to the growth phase was observed at 24 h, with aggregates exceeding ∼60 nm undergoing irreversible fibrillization. The ZIF-8-modified electrochemical sensor detected early-stage structural rearrangements with superior sensitivity compared to conventional ThT fluorescence, revealing subtle oligomer formation. Quantitative current measurements allowed continuous monitoring of aggregation kinetics, highlighting the temporal resolution of the platform. Validation experiments with curcumin treatment demonstrated strong inhibitory effects between 18 and 24 h, delaying fibrillization, reducing late-stage β-sheet accumulation, and decreasing aggregate size by approximately 25%. In addition, the sensor successfully distinguished minor differences in structural transitions under varying inhibitor concentrations, demonstrating its capability for high-resolution, real-time assessment of aggregation dynamics and drug efficacy. This ZIF-8-modified electrochemical biosensor provides high-sensitivity, dynamic monitoring of Aβ42 aggregation and drug-induced inhibition, offering a valuable tool for mechanistic studies of protein aggregation pathology. By enabling early detection of structural transitions and real-time evaluation of inhibitors, this platform has the potential to accelerate therapeutic screening and improve the development of effective interventions for AD.