Familial Alzheimer’s Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates
Amyloid-beta (Aβ) deposition as senile plaques is a pathological hallmark of Alzheimer's disease (AD). AD is characterized by a large level of heterogeneity in amyloid pathology, whose molecular origin is poorly understood. Here, we employ NMR spectroscopy and MD simulation at ambient and high...
Published in: | The Journal of Physical Chemistry Letters |
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ftfzjuelichnvdb:oai:juser.fz-juelich.de:996736 2023-10-29T02:34:25+01:00 Familial Alzheimer’s Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates Rezaei-Ghaleh, Nasrollah Amininasab, Mehriar Giller, Karin Becker, Stefan DE 2023 https://juser.fz-juelich.de/record/996736 https://juser.fz-juelich.de/search?p=id:%22FZJ-2023-01152%22 eng eng ACS info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jpclett.2c03729 info:eu-repo/semantics/altIdentifier/hdl/2128/33875 info:eu-repo/semantics/altIdentifier/pmid/36734539 info:eu-repo/semantics/altIdentifier/issn/1948-7185 info:eu-repo/semantics/altIdentifier/wos/WOS:000928873500001 https://juser.fz-juelich.de/record/996736 https://juser.fz-juelich.de/search?p=id:%22FZJ-2023-01152%22 info:eu-repo/semantics/openAccess The journal of physical chemistry letters 14, 1427 - 1435 (2023). doi:10.1021/acs.jpclett.2c03729 info:eu-repo/classification/ddc/530 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2023 ftfzjuelichnvdb https://doi.org/10.1021/acs.jpclett.2c03729 2023-10-01T22:17:56Z Amyloid-beta (Aβ) deposition as senile plaques is a pathological hallmark of Alzheimer's disease (AD). AD is characterized by a large level of heterogeneity in amyloid pathology, whose molecular origin is poorly understood. Here, we employ NMR spectroscopy and MD simulation at ambient and high pressures and investigate how AD-related mutations in Aβ peptide influence the stability of Aβ aggregates. The pressure-induced monomer dissociation from Aβ aggregates monitored by NMR demonstrated that the Iowa (D23N), Arctic (E22G), and Osaka (ΔE22) mutations altered the pressure stability of Aβ40 aggregates in distinct manners. While the NMR data of monomeric Aβ40 showed only small localized effects of mutations, the MD simulation of mutated Aβ fibrils revealed their distinct susceptibility to elevated pressure. Our data propose a structural basis for the distinct stability of various Aβ fibrils and highlights "stability" as a molecular property potentially contributing to the large heterogeneity of amyloid pathology in AD. Article in Journal/Newspaper Arctic Forschungszentrum Jülich: JuSER (Juelich Shared Electronic Resources) The Journal of Physical Chemistry Letters 14 6 1427 1435 |
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Forschungszentrum Jülich: JuSER (Juelich Shared Electronic Resources) |
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language |
English |
topic |
info:eu-repo/classification/ddc/530 |
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info:eu-repo/classification/ddc/530 Rezaei-Ghaleh, Nasrollah Amininasab, Mehriar Giller, Karin Becker, Stefan Familial Alzheimer’s Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates |
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info:eu-repo/classification/ddc/530 |
description |
Amyloid-beta (Aβ) deposition as senile plaques is a pathological hallmark of Alzheimer's disease (AD). AD is characterized by a large level of heterogeneity in amyloid pathology, whose molecular origin is poorly understood. Here, we employ NMR spectroscopy and MD simulation at ambient and high pressures and investigate how AD-related mutations in Aβ peptide influence the stability of Aβ aggregates. The pressure-induced monomer dissociation from Aβ aggregates monitored by NMR demonstrated that the Iowa (D23N), Arctic (E22G), and Osaka (ΔE22) mutations altered the pressure stability of Aβ40 aggregates in distinct manners. While the NMR data of monomeric Aβ40 showed only small localized effects of mutations, the MD simulation of mutated Aβ fibrils revealed their distinct susceptibility to elevated pressure. Our data propose a structural basis for the distinct stability of various Aβ fibrils and highlights "stability" as a molecular property potentially contributing to the large heterogeneity of amyloid pathology in AD. |
format |
Article in Journal/Newspaper |
author |
Rezaei-Ghaleh, Nasrollah Amininasab, Mehriar Giller, Karin Becker, Stefan |
author_facet |
Rezaei-Ghaleh, Nasrollah Amininasab, Mehriar Giller, Karin Becker, Stefan |
author_sort |
Rezaei-Ghaleh, Nasrollah |
title |
Familial Alzheimer’s Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates |
title_short |
Familial Alzheimer’s Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates |
title_full |
Familial Alzheimer’s Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates |
title_fullStr |
Familial Alzheimer’s Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates |
title_full_unstemmed |
Familial Alzheimer’s Disease-Related Mutations Differentially Alter Stability of Amyloid-Beta Aggregates |
title_sort |
familial alzheimer’s disease-related mutations differentially alter stability of amyloid-beta aggregates |
publisher |
ACS |
publishDate |
2023 |
url |
https://juser.fz-juelich.de/record/996736 https://juser.fz-juelich.de/search?p=id:%22FZJ-2023-01152%22 |
op_coverage |
DE |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
The journal of physical chemistry letters 14, 1427 - 1435 (2023). doi:10.1021/acs.jpclett.2c03729 |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jpclett.2c03729 info:eu-repo/semantics/altIdentifier/hdl/2128/33875 info:eu-repo/semantics/altIdentifier/pmid/36734539 info:eu-repo/semantics/altIdentifier/issn/1948-7185 info:eu-repo/semantics/altIdentifier/wos/WOS:000928873500001 https://juser.fz-juelich.de/record/996736 https://juser.fz-juelich.de/search?p=id:%22FZJ-2023-01152%22 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1021/acs.jpclett.2c03729 |
container_title |
The Journal of Physical Chemistry Letters |
container_volume |
14 |
container_issue |
6 |
container_start_page |
1427 |
op_container_end_page |
1435 |
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1781056998825000960 |