Hedgehog-nanovesicles redox probe based “explosive” signal amplification biosensing platform for Alzheimer's disease early diagnosis

Plasma brain-derived extracellular vesicles (BDEVs) possess excellent potential for the early diagnosis of Alzheimer's disease (AD). However, their accurate detection is often trapped by the low levels of specific BDEVs and the serious interference of high abundance surface proteins on EVs. In this study, an explosive signal amplification biosensing platform based on the novel “hedgehog-nanovesicles redox probe” was developed for the ultra-sensitive detection of plasma BDEVs. The novel probe was self-assembled by the target BDEVs, and it immobilized by methylene blue-conjugated aptamers, which enabled a dual-signal ratiometric sensor. Owing to the multi-amplification capability of novel probe and the built-in correction factor of dual-signal, the proposed platform exhibited higher sensitivity (with a limit of detection of 2.63 × 10 2 particles/mL), non-specific interferences, simpler operation, and more efficient preparation than previous methods. In the analysis of clinical samples, AD and mild cognitive impairment (MCI) patients can be differentiated from healthy individuals with AUC values of 0.823 and 0.833. The diagnostic accuracy of AD and MCI can be significantly improved with AUC values of 0.963 and 0.949 after combined with plasma Aβ42/Aβ40. It confirmed that BDEVs possess strong potential for AD early diagnosis, and particularly the sensor strategy provided a powerful tool for this purpose.