Alzheimer's Disease (AD) is a neurodegenerative disease, of which β-amyloid (Aβ) deposition is one of the most important pathological features. It has been reported that during Aβ aggregation, the microenvironment around the Aβ protein is altered in terms of viscosity and polarity. In this work, we developed five novel hemicyanine fluorescent probes (MZs). After screening the photochemical properties, MZ-2 and 3 were found to enable the rapid detection of Aβ aggregates, which were also sensitive to ambient viscosity. After comparison the structure of probes, we also observed that extensions of conjugated π-systems effectively cause redshifts of excitation wavelength. In the meanwhile, hydroxyl groups with weaker ionization strengths are more responsive to Aβ aggregates than sulfonate groups, probably due to the small size of the hydroxyl group and the acidity. Overall, MZ-2 showed the best response to Aβ aggregates (15.35-fold) and viscosity (17.6-fold). MZ-2 can quickly cross the blood-brain barrier (BBB), enabling high-fidelity imaging of Aβ aggregates in the mice brain.
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