CRISPR/Cas12a-Mediated Electrochemical Aptasensor for Simultaneous Determination of Alzheimer’s Disease Biomarkers in Human Blood

Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disease, and the ratio of 40 and 42 residue amyloid beta peptides (Aβ40 and Aβ42) plays a crucial role as a biomarker for the early diagnosis of AD. Conventional laboratory-based assays for Aβ proteins analysis typically relies on the collection of cerebrospinal fluid (CSF). In contrast, blood samples offer a less invasive alternative but present challenges due to lower concentrations of Aβ. This study presents a novel strategy that combines aptamer-specific recognition with CRISPR/Cas12a-mediated signal amplification in an electrochemical sensing platform. The proposed electrochemical sensing platform achieved reliable and accurate results when applied to clinical serum samples, validating its effectiveness in practical scenarios. This approach enables highly specific detection of Aβ40 and Aβ42 with detection limits as low as 1.1 and 0.8 pg/mL, respectively. Moreover, the platform demonstrated outstanding repeatability and operational stability, underscoring its potential as a robust and highly sensitive diagnostic tool for the early detection of AD.