Unique molecular signatures of Alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation
The formation of amyloid β (Aβ) peptide aggregates, oligomers, and fibrils is a dynamic process; however, the kinetics of their formation is not well understood. This study compares the time course of aggregate/fibril formation by transmission electron microscopy (TEM) analyses with that of oligomer...
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crwiley:10.1002/jnr.23507 2024-06-02T08:01:44+00:00 Unique molecular signatures of Alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation Poduslo, Joseph F. Howell, Kyle G. 2014 http://dx.doi.org/10.1002/jnr.23507 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjnr.23507 https://onlinelibrary.wiley.com/doi/pdf/10.1002/jnr.23507 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Journal of Neuroscience Research volume 93, issue 3, page 410-423 ISSN 0360-4012 1097-4547 journal-article 2014 crwiley https://doi.org/10.1002/jnr.23507 2024-05-03T11:47:39Z The formation of amyloid β (Aβ) peptide aggregates, oligomers, and fibrils is a dynamic process; however, the kinetics of their formation is not well understood. This study compares the time course of aggregate/fibril formation by transmission electron microscopy (TEM) analyses with that of oligomer/fibril formation by Western blot analysis under native and denaturing conditions. Efforts to deaggregate/defibrillate these peptides by using hexafluoroisopropanol, ammonium hydroxide, or dimethylsulfoxide did not change the nondenaturing polyacrylamide gel electrophoresis (PAGE) footprints or drive the peptides to a monomeric species. Regardless of the pretreatment protocol, TEM analyses reveal that all Aβ peptides (Aβ40, Aβ42, Aβ39E22Δ [Osaka], Aβ40E22G [Arctic], Aβ40E22Q [Dutch], and Aβ40A2T [Icelandic]) immediately formed nonfibrillar, amorphous aggregates when first placed into solution with the Osaka mutation, quickly forming early‐stage fibrils. The extent of fibril formation for other Aβ peptides is time dependent, with the Arctic mutation forming fibrils at 1 hr, the Dutch and Icelandic at 4 hr, Aβ42 at 8 hr, and Aβ40 at 24 hr. In contrast, nondenaturing PAGE revealed unique footprints for the different Aβ species. The rapidity of aggregate formation and the rapid transition to fibrils, particularly for the Osaka deletion, suggest an important role for aggregates/fibrils of Aβ in the development of neuronal degeneration. © 2014 Wiley Periodicals, Inc. Article in Journal/Newspaper Arctic Wiley Online Library Arctic Journal of Neuroscience Research 93 3 410 423 |
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description |
The formation of amyloid β (Aβ) peptide aggregates, oligomers, and fibrils is a dynamic process; however, the kinetics of their formation is not well understood. This study compares the time course of aggregate/fibril formation by transmission electron microscopy (TEM) analyses with that of oligomer/fibril formation by Western blot analysis under native and denaturing conditions. Efforts to deaggregate/defibrillate these peptides by using hexafluoroisopropanol, ammonium hydroxide, or dimethylsulfoxide did not change the nondenaturing polyacrylamide gel electrophoresis (PAGE) footprints or drive the peptides to a monomeric species. Regardless of the pretreatment protocol, TEM analyses reveal that all Aβ peptides (Aβ40, Aβ42, Aβ39E22Δ [Osaka], Aβ40E22G [Arctic], Aβ40E22Q [Dutch], and Aβ40A2T [Icelandic]) immediately formed nonfibrillar, amorphous aggregates when first placed into solution with the Osaka mutation, quickly forming early‐stage fibrils. The extent of fibril formation for other Aβ peptides is time dependent, with the Arctic mutation forming fibrils at 1 hr, the Dutch and Icelandic at 4 hr, Aβ42 at 8 hr, and Aβ40 at 24 hr. In contrast, nondenaturing PAGE revealed unique footprints for the different Aβ species. The rapidity of aggregate formation and the rapid transition to fibrils, particularly for the Osaka deletion, suggest an important role for aggregates/fibrils of Aβ in the development of neuronal degeneration. © 2014 Wiley Periodicals, Inc. |
format |
Article in Journal/Newspaper |
author |
Poduslo, Joseph F. Howell, Kyle G. |
spellingShingle |
Poduslo, Joseph F. Howell, Kyle G. Unique molecular signatures of Alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation |
author_facet |
Poduslo, Joseph F. Howell, Kyle G. |
author_sort |
Poduslo, Joseph F. |
title |
Unique molecular signatures of Alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation |
title_short |
Unique molecular signatures of Alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation |
title_full |
Unique molecular signatures of Alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation |
title_fullStr |
Unique molecular signatures of Alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation |
title_full_unstemmed |
Unique molecular signatures of Alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation |
title_sort |
unique molecular signatures of alzheimer's disease amyloid β peptide mutations and deletion during aggregate/oligomer/fibril formation |
publisher |
Wiley |
publishDate |
2014 |
url |
http://dx.doi.org/10.1002/jnr.23507 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjnr.23507 https://onlinelibrary.wiley.com/doi/pdf/10.1002/jnr.23507 |
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Arctic |
geographic_facet |
Arctic |
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Arctic |
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Arctic |
op_source |
Journal of Neuroscience Research volume 93, issue 3, page 410-423 ISSN 0360-4012 1097-4547 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/jnr.23507 |
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Journal of Neuroscience Research |
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93 |
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3 |
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410 |
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423 |
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