DNA- and aptamer-based biosensors for Alzheimer's disease biomarkers toward clinical translation

Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which early diagnosis remains a major challenge. DNA-based biosensors and aptamer-based biosensors have emerged as complementary platforms for the sensitive and selective detection of Alzheimer's disease biomarkers. DNA biosensors primarily detect nucleic acid biomarkers, including disease-associated microRNAs, through sequence-specific hybridization, whereas aptamer-based biosensors are mainly employed for the recognition of protein biomarkers such as amyloid-β and tau proteins. Recent advances in nanomaterials have significantly enhanced biosensor performance by improving target recognition, signal amplification, and analytical sensitivity. This review summarizes recent developments in both DNA hybridization-based biosensors and aptamer-based biosensors for Alzheimer's disease biomarkers, highlighting their distinct recognition mechanisms, sensing strategies, and applications in electrochemical, optical, fluorescence, and nanomaterial-assisted platforms. Representative systems are compared in terms of analytical performance, detection limit, selectivity, and applicability to biological samples. Current challenges related to reproducibility, matrix interference, standardization, and clinical validation are also discussed. Despite remarkable progress, further efforts are required to translate these technologies into robust and reliable point-of-care diagnostic tools. The integration of advanced nanomaterials, DNA nanotechnology, and multiplexed sensing platforms is expected to accelerate the clinical implementation of biosensors for early AD diagnosis.