Development of Aryl Cyano Amides for Fluorescence Discrimination of Tau and Amyloid Beta Deposits in Tissue

The accumulation of amyloid aggregates such as amyloid beta (Aβ) and tau deposits in the brain is a hallmark of many neurodegenerative diseases including Alzheimer's disease. Recent advances in optical imaging have shown that fluorescent probes can detect amyloids in living patients, potentially aiding in diagnosis. Here, we investigate structural modifications of amyloid-targeting Aryl Cyano Amide-based fluorophores aimed at enhancing their ability to discriminate between different amyloid aggregates, such as Aβ and tau. We identify two structural parameters that synergistically enable increased sensitivity to environmental polarity, which makes it possible to discriminate these amyloids through inspection of the color of fluorescence emission. This colorimetric discrimination can provide detailed information on amyloid composition and could expand the use of fluorescence imaging for diagnosis and monitoring of neurodegenerative diseases.