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EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains

In neurodegenerative diseases, proteins fold into amyloid structures with distinct conformations (strains) that are characteristic of different diseases. However, there is a need to rapidly identify amyloid conformations in situ. Here, we use machine learning on the full information available in flu...

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Autores principales: Yang, Hyunjun, Yuan, Peng, Wu, Yibing, Shi, Marie, Caro, Christoffer D., Tengeiji, Atsushi, Yamanoi, Shigeo, Inoue, Masahiro, DeGrado, William F., Condello, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041141/
https://www.ncbi.nlm.nih.gov/pubmed/36927157
http://dx.doi.org/10.1073/pnas.2300769120
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author Yang, Hyunjun
Yuan, Peng
Wu, Yibing
Shi, Marie
Caro, Christoffer D.
Tengeiji, Atsushi
Yamanoi, Shigeo
Inoue, Masahiro
DeGrado, William F.
Condello, Carlo
author_facet Yang, Hyunjun
Yuan, Peng
Wu, Yibing
Shi, Marie
Caro, Christoffer D.
Tengeiji, Atsushi
Yamanoi, Shigeo
Inoue, Masahiro
DeGrado, William F.
Condello, Carlo
author_sort Yang, Hyunjun
collection PubMed
description In neurodegenerative diseases, proteins fold into amyloid structures with distinct conformations (strains) that are characteristic of different diseases. However, there is a need to rapidly identify amyloid conformations in situ. Here, we use machine learning on the full information available in fluorescent excitation/emission spectra of amyloid-binding dyes to identify six distinct different conformational strains in vitro, as well as amyloid-β (Aβ) deposits in different transgenic mouse models. Our EMBER (excitation multiplexed bright emission recording) imaging method rapidly identifies conformational differences in Aβ and tau deposits from Down syndrome, sporadic and familial Alzheimer’s disease human brain slices. EMBER has in situ identified distinct conformational strains of tau inclusions in astrocytes, oligodendrocytes, and neurons from Pick’s disease. In future studies, EMBER should enable high-throughput measurements of the fidelity of strain transmission in cellular and animal neurodegenerative diseases models, time course of amyloid strain propagation, and identification of pathogenic versus benign strains.
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spelling pubmed-100411412023-03-28 EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains Yang, Hyunjun Yuan, Peng Wu, Yibing Shi, Marie Caro, Christoffer D. Tengeiji, Atsushi Yamanoi, Shigeo Inoue, Masahiro DeGrado, William F. Condello, Carlo Proc Natl Acad Sci U S A Biological Sciences In neurodegenerative diseases, proteins fold into amyloid structures with distinct conformations (strains) that are characteristic of different diseases. However, there is a need to rapidly identify amyloid conformations in situ. Here, we use machine learning on the full information available in fluorescent excitation/emission spectra of amyloid-binding dyes to identify six distinct different conformational strains in vitro, as well as amyloid-β (Aβ) deposits in different transgenic mouse models. Our EMBER (excitation multiplexed bright emission recording) imaging method rapidly identifies conformational differences in Aβ and tau deposits from Down syndrome, sporadic and familial Alzheimer’s disease human brain slices. EMBER has in situ identified distinct conformational strains of tau inclusions in astrocytes, oligodendrocytes, and neurons from Pick’s disease. In future studies, EMBER should enable high-throughput measurements of the fidelity of strain transmission in cellular and animal neurodegenerative diseases models, time course of amyloid strain propagation, and identification of pathogenic versus benign strains. National Academy of Sciences 2023-03-16 2023-03-21 /pmc/articles/PMC10041141/ /pubmed/36927157 http://dx.doi.org/10.1073/pnas.2300769120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Yang, Hyunjun
Yuan, Peng
Wu, Yibing
Shi, Marie
Caro, Christoffer D.
Tengeiji, Atsushi
Yamanoi, Shigeo
Inoue, Masahiro
DeGrado, William F.
Condello, Carlo
EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains
title EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains
title_full EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains
title_fullStr EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains
title_full_unstemmed EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains
title_short EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains
title_sort ember multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041141/
https://www.ncbi.nlm.nih.gov/pubmed/36927157
http://dx.doi.org/10.1073/pnas.2300769120
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