The development of a highly sensitive electrochemical aptasensor is reported that combines the unique properties of graphene, metallic oxides, and conducting polymers to overcome the limitations of sensitivity and specificity required for early diagnosis of Alzheimer’s desease (AD). The sensor design utilizes a ternary composite of polypyrrole (PPy), reduced graphene oxide (rGO), and Fe₂O₃ nanoparticles, which synergistically enhance signal amplification, conductivity, and biocompatibility. The aptasensor leverages aptamers as biorecognition elements for the specific detection of Aβ1-40 oligomers. Electrochemical techniques, including cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS), were employed to characterize and evaluate the sensor’s performance. The fabricated aptasensor demonstrated an extraordinary detection limit of 40 fM and a broad linear detection range from 0.1 pM to 200 nM, with exceptional sensitivity and selectivity. Furthermore, the sensor exhibited excellent reproducibility and stability, essential for real-world clinical applications. Real-sample testing using artificial serum further validated the aptasensor’s reliability, showcasing its potential for early diagnosis and monitoring of AD. The robust platform and modular design of the sensor also pave the way for its adaptation to detect other target biomolecules by simply modifying the aptamer. This work represents a significant advancement in biosensor technology, offering a versatile, highly sensitive tool for biomedical diagnostics and personalized medicine.© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.