Finding a timely, sensitive, and noninvasive detection
method has
become an urgent need for asymptomatic early diagnosis of Alzheimer’s
disease (AD). MicroRNA-193b (miR-193b) and Aβ42 oligomers (AβO42)
in neurogenic exosomes were confirmed to reflect pathological changes
in the AD early stage. The combination of two biomarkers is promising
for the earlier detection of AD. In this study, a detection system
based on the principle of the entropy-driven strand displacement reaction
(ESDR) was developed, including a dumbbell detection probe (H), an
indicator probe (R), and graphene oxide (GO). In the detection system,
the two hairpins of H were opened by the interaction of miR-193b (T1)
and AβO42 (T2) with the aptamer. Then R hybridized with H and
began to displace T, initiating the next round of ESDR to achieve
sensitive detection of T. GO specifically adsorbed free R and quenched
the fluorescence, further reducing the intensity of the background
signal. Both of these points provided the system with a more sensitive
analytical performance. The detection limit of miR-193b was 77 pM
and the detection limit of AβO42 was 53 pM. This sensor detected
the change of “one increase (AβO42) and one decrease
(miR-193b)” in the exosome sample. Additionally, results showed
that this detection system could distinguish the model of early AD
from the non-AD control, which was sufficient for earlier and more
sensitive detection of AD. This strategy has strong specificity, high
sensitivity, and easy operation, which provides broad prospects for
the early diagnosis of AD.