A Coumarin-Based Array for the Discrimination of Amyloids
Natalie Trinh, Kaustubh R. Bhuskute, Nikhil R. Varghese, Jessica A. Buchanan, Yijia Xu, Fiona McCutcheon, Robert L. Medcalf, Katrina A. Jolliffe, Margaret Sunde, Elizabeth J. New, Amandeep Kaur
Abstract
Self-assembly of misfolded proteins can lead to the formation of amyloids, which are implicated in the onset of many pathologies including Alzheimer's disease and Parkinson's disease. The facile detection and discrimination of different amyloids are crucial for early diagnosis of amyloid-related pathologies. Here, we report the development of a fluorescent coumarin-based two-sensor array that is able to correctly discriminate between four different amyloids implicated in amyloid-related pathologies with 100% classification. The array was also applied to mouse models of Alzheimer's disease and was able to discriminate between samples from mice corresponding to early (6 months) and advanced (12 months) stages of Alzheimer's disease. Finally, the flexibility of the array was assessed by expanding the analytes to include functional amyloids. The same two-sensor array was able to correctly discriminate between eight different disease-associated and functional amyloids with 100% classification.