Extracellular vesicle-based point-of-care testing for diagnosis and monitoring of Alzheimer's disease.

Abstract

Extracellular vesicles (EVs) show potential for early diagnosis of Alzheimer's disease (AD) and monitoring of its progression. However, EV-based AD diagnosis faces challenges due to the small size and low abundance of biomarkers. Here, we report a fully integrated organic electrochemical transistor (OECT) sensor for ultrafast, accurate, and convenient point-of-care testing (POCT) of serum EVs from AD patients. By utilizing acoustoelectric enrichment, the EVs can be quickly propelled, significantly enriched, and specifically bound to the OECT detection area, achieving a gain of over 280 times response in 30 s. The integrated POCT sensor can detect serum EVs from AD patients with a limit of detection as low as 500 EV particles/mL and a reduced detection time of just two minutes. Furthermore, the integrated POCT sensors were used to monitor AD progression in an AD mouse model by testing the mouse Aβ EVs at different time courses (up to 18 months) and compared with the Aβ accumulation using high-resolution magnetic resonance imaging (MRI). This innovative technology has the potential for accurate and rapid diagnosis of Alzheimer's and other neurodegenerative diseases, and monitoring of disease progression and treatment response.