Ultrasensitive extracellular vesicles-associated amyloid-β1-42 oligomers analytical platform for early diagnosis of Alzheimer's disease.

Extracellular vesicles (EVs) are increasingly recognized as promising biomarkers for central nervous system diseases, including Alzheimer's disease (AD). However, early and accurate AD diagnosis remains challenging due to the extremely low abundance of relevant biomarkers in body fluids. Here, we present an ultrasensitive and reliable platform for quantifying trace levels of EVs-associated Aβ1-42 oligomers (EVs@Aβ1-42) in plasma. The method integrates UiO-66-B(OH)2 nanomaterials for high-efficiency enrichment of EVs with the i-SQM "turn-on" fluorescent probe, which selectively responds to Aβ1-42 oligomers. This combined strategy enables rapid quantification within minutes and provides a large fluorescence enhancement with excellent signal-to-noise ratio, achieving femtomolar-level sensitivity. In clinical samples, the platform successfully distinguishes AD patients from cognitively normal individuals with 100 % sensitivity and 96.3 % specificity. Overall, this EVs-based detection system offers a practical, low-cost, and non-invasive approach for plasma biomarker analysis and holds strong potential for early AD diagnosis.