Multifunctional Hemicyanine Probes for Early Alzheimer's Detection via Aβ Aggregates

Alzheimer's Disease (AD) is an irreversible neurodegenerative disorder, and currently, there is a lack of effective early diagnostic methods and therapeutic approaches. Abnormal accumulation of amyloid-β (Aβ) is one of the core biomarkers for the occurrence and progression of AD. This study introduces NS and NSS, two multifunctional probes designed and synthesized from a hemicyanine framework. These probes utilize N, N-diethyl aniline as the electron donor and thiophene groups as the π-bridge, enabling the specific fluorescence enhancement responses to Aβ oligomers and fibrils. We initially expected that increasing the conjugation length would redshift the emission wavelength; however, NSS, with one more thiophene unit than NS, showed a spectral shift of less than 10 nm but a significantly decreased responsiveness, demonstrating that the molecular length of hemicyanine framework greatly influences their Aβ-binding performance. In vitro and in vivo experimental results show that NS can rapidly cross the blood-brain barrier and precisely detect Aβ deposits in transgenic mouse models. This study introduces an innovative methodology for constructing integrated diagnostic probes, representing a significant advancement in the early identification of AD pathology.