A Coumarin-Based Array for the Discrimination of Amyloids

Natalie Trinh; Kaustubh R. Bhuskute; Nikhil R. Varghese; Jessica A. Buchanan; Yijia Xu; Fiona M. McCutcheon; Robert L. Medcalf; Katrina A. Jolliffe; Margaret Sunde; Elizabeth J. New; Amandeep Kaur

doi:10.1021/acssensors.3c01334

A Coumarin-Based Array for the Discrimination of Amyloids

Natalie Trinh, Kaustubh R. Bhuskute, Nikhil R. Varghese, Jessica A. Buchanan, Yijia Xu, Fiona M. McCutcheon, Robert L. Medcalf, Katrina A. Jolliffe, Margaret Sunde, Elizabeth J. New, Amandeep Kaur

Research output: Contribution to journal › Article › Research › peer-review

2 Citations (Scopus)

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.

Original language	English
Pages (from-to)	615–621
Number of pages	7
Journal	ACS Sensors
Volume	9
Issue number	2
DOIs	https://doi.org/10.1021/acssensors.3c01334
Publication status	Published - 23 Feb 2024

Keywords

Alzheimer’s disease
amyloids
fluorescence
linear discriminant analysis
sensing array

Access to Document

10.1021/acssensors.3c01334

Cite this

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title = "A Coumarin-Based Array for the Discrimination of Amyloids",

abstract = "Self-assembly of misfolded proteins can lead to the formation of amyloids, which are implicated in the onset of many pathologies including Alzheimer{\textquoteright}s disease and Parkinson{\textquoteright}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{\textquoteright}s disease and was able to discriminate between samples from mice corresponding to early (6 months) and advanced (12 months) stages of Alzheimer{\textquoteright}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.",

keywords = "Alzheimer{\textquoteright}s disease, amyloids, fluorescence, linear discriminant analysis, sensing array",

author = "Natalie Trinh and Bhuskute, {Kaustubh R.} and Varghese, {Nikhil R.} and Buchanan, {Jessica A.} and Yijia Xu and McCutcheon, {Fiona M.} and Medcalf, {Robert L.} and Jolliffe, {Katrina A.} and Margaret Sunde and New, {Elizabeth J.} and Amandeep Kaur",

note = "Funding Information: The authors would like to acknowledge the Australian Research Council (CE200100012, DP180101353, DE210101176, and DP200102463) and the National Health and Medical Research Council (APP1156506) for funding and the Australian Government for Research Training Program Scholarships (N.T., N.R.V., J.A.B., and F.M.M.). We acknowledge the scientific and technical assistance of the Sydney Analytical Core Research Facility at the University of Sydney, and Dr Jason Dang in the Monash Spectroscopy Facility. Graphical abstract created using BioRender. Publisher Copyright: {\textcopyright} 2024 American Chemical Society.",

year = "2024",

month = feb,

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doi = "10.1021/acssensors.3c01334",

language = "English",

volume = "9",

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journal = "ACS Sensors",

issn = "2379-3694",

publisher = "American Chemical Society",

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AU - Trinh, Natalie

AU - Bhuskute, Kaustubh R.

AU - Varghese, Nikhil R.

AU - Buchanan, Jessica A.

AU - Xu, Yijia

AU - McCutcheon, Fiona M.

AU - Medcalf, Robert L.

AU - Jolliffe, Katrina A.

AU - Sunde, Margaret

AU - New, Elizabeth J.

AU - Kaur, Amandeep

N1 - Funding Information: The authors would like to acknowledge the Australian Research Council (CE200100012, DP180101353, DE210101176, and DP200102463) and the National Health and Medical Research Council (APP1156506) for funding and the Australian Government for Research Training Program Scholarships (N.T., N.R.V., J.A.B., and F.M.M.). We acknowledge the scientific and technical assistance of the Sydney Analytical Core Research Facility at the University of Sydney, and Dr Jason Dang in the Monash Spectroscopy Facility. Graphical abstract created using BioRender. Publisher Copyright: © 2024 American Chemical Society.

PY - 2024/2/23

Y1 - 2024/2/23

N2 - 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.

AB - 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.

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A Coumarin-Based Array for the Discrimination of Amyloids

Abstract

Keywords

Access to Document

Other files and links

Fluorescent probes for super-resolution imaging of the amyloid architecture

ARC Centre of Excellence for Innovations in Peptide and Protein Science

Improving the safety and predictable efficacy of thrombolytic therapy in acute ischaemic stroke

Cite this

A Coumarin-Based Array for the Discrimination of Amyloids

Abstract

Keywords

Access to Document

Other files and links

Projects

Fluorescent probes for super-resolution imaging of the amyloid architecture

ARC Centre of Excellence for Innovations in Peptide and Protein Science

Improving the safety and predictable efficacy of thrombolytic therapy in acute ischaemic stroke

Cite this