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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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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. |
format | Online Article Text |
id | pubmed-10041141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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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