Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM
Morphology of aggregation intermediates, polymorphism of amyloid fibrils and aggregation kinetics of the "Arctic" mutant of the Alzheimer's amyloid β-peptide, Aβ(1-40)(E22G), in a physiologically relevant Tris buffer (pH 7.4) were thoroughly explored in comparison with the human wild...
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ftneicon:oai:rour.neicon.ru:rour/177121 2023-05-15T14:56:53+02:00 Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM Norlin N. Hellberg M. Filippov A. Sousa A. Gröbner G. Leapman R. Almqvist N. Antzutkin O. 2012 https://openrepository.ru/article?id=177121 unknown Journal of Structural Biology 1 180 174 http://rour.neicon.ru:80/xmlui/bitstream/rour/177121/1/nora.pdf 1047-8477 https://openrepository.ru/article?id=177121 SCOPUS10478477-2012-180-1-SID84866988080 AFM Amyloid β-peptide Arctic mutation CD Mass-per-length measurements Polymorphism of amyloid fibrils Real time growth Spherical aggregates STEM TEM ThT assay Article 2012 ftneicon 2020-07-21T12:00:03Z Morphology of aggregation intermediates, polymorphism of amyloid fibrils and aggregation kinetics of the "Arctic" mutant of the Alzheimer's amyloid β-peptide, Aβ(1-40)(E22G), in a physiologically relevant Tris buffer (pH 7.4) were thoroughly explored in comparison with the human wild type Alzheimer's amyloid peptide, wt-Aβ(1-40), using both in situ atomic force and electron microscopy, circular dichroism and thioflavin T fluorescence assays. For arc-Aβ(1-40) at the end of the 'lag'-period of fibrillization an abrupt appearance of ∼3nm size 'spherical aggregates' with a homogeneous morphology, was identified. Then, the aggregation proceeds with a rapid growth of amyloid fibrils with a variety of morphologies, while the spherical aggregates eventually disappeared during in situ measurements. Arc-Aβ(1-40) was also shown to form fibrils at much lower concentrations than wt-Aβ(1-40): ≤2.5μM and 12.5μM, respectively. Moreover, at the same concentration, 50μM, the aggregation process proceeds more rapidly for arc-Aβ(1-40): the first amyloid fibrils were observed after c.a. 72h from the onset of incubation as compared to approximately 7days for wt-Aβ(1-40). Amyloid fibrils of arc-Aβ(1-40) exhibit a large variety of polymorphs, at least five, both coiled and non-coiled distinct fibril structures were recognized by AFM, while at least four types of arc-Aβ(1-40) fibrils were identified by TEM and STEM and their mass-per-length statistics were collected suggesting supramolecular structures with two, four and six β-sheet laminae. Our results suggest a pathway of fibrillogenesis for full-length Alzheimer's peptides with small and structurally ordered transient spherical aggregates as on-pathway immediate precursors of amyloid fibrils. © 2012 Elsevier Inc. Article in Journal/Newspaper Arctic NORA (National aggregator of open repositories of Russian universities) Arctic |
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Open Polar |
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NORA (National aggregator of open repositories of Russian universities) |
op_collection_id |
ftneicon |
language |
unknown |
topic |
AFM Amyloid β-peptide Arctic mutation CD Mass-per-length measurements Polymorphism of amyloid fibrils Real time growth Spherical aggregates STEM TEM ThT assay |
spellingShingle |
AFM Amyloid β-peptide Arctic mutation CD Mass-per-length measurements Polymorphism of amyloid fibrils Real time growth Spherical aggregates STEM TEM ThT assay Norlin N. Hellberg M. Filippov A. Sousa A. Gröbner G. Leapman R. Almqvist N. Antzutkin O. Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM |
topic_facet |
AFM Amyloid β-peptide Arctic mutation CD Mass-per-length measurements Polymorphism of amyloid fibrils Real time growth Spherical aggregates STEM TEM ThT assay |
description |
Morphology of aggregation intermediates, polymorphism of amyloid fibrils and aggregation kinetics of the "Arctic" mutant of the Alzheimer's amyloid β-peptide, Aβ(1-40)(E22G), in a physiologically relevant Tris buffer (pH 7.4) were thoroughly explored in comparison with the human wild type Alzheimer's amyloid peptide, wt-Aβ(1-40), using both in situ atomic force and electron microscopy, circular dichroism and thioflavin T fluorescence assays. For arc-Aβ(1-40) at the end of the 'lag'-period of fibrillization an abrupt appearance of ∼3nm size 'spherical aggregates' with a homogeneous morphology, was identified. Then, the aggregation proceeds with a rapid growth of amyloid fibrils with a variety of morphologies, while the spherical aggregates eventually disappeared during in situ measurements. Arc-Aβ(1-40) was also shown to form fibrils at much lower concentrations than wt-Aβ(1-40): ≤2.5μM and 12.5μM, respectively. Moreover, at the same concentration, 50μM, the aggregation process proceeds more rapidly for arc-Aβ(1-40): the first amyloid fibrils were observed after c.a. 72h from the onset of incubation as compared to approximately 7days for wt-Aβ(1-40). Amyloid fibrils of arc-Aβ(1-40) exhibit a large variety of polymorphs, at least five, both coiled and non-coiled distinct fibril structures were recognized by AFM, while at least four types of arc-Aβ(1-40) fibrils were identified by TEM and STEM and their mass-per-length statistics were collected suggesting supramolecular structures with two, four and six β-sheet laminae. Our results suggest a pathway of fibrillogenesis for full-length Alzheimer's peptides with small and structurally ordered transient spherical aggregates as on-pathway immediate precursors of amyloid fibrils. © 2012 Elsevier Inc. |
format |
Article in Journal/Newspaper |
author |
Norlin N. Hellberg M. Filippov A. Sousa A. Gröbner G. Leapman R. Almqvist N. Antzutkin O. |
author_facet |
Norlin N. Hellberg M. Filippov A. Sousa A. Gröbner G. Leapman R. Almqvist N. Antzutkin O. |
author_sort |
Norlin N. |
title |
Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM |
title_short |
Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM |
title_full |
Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM |
title_fullStr |
Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM |
title_full_unstemmed |
Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM |
title_sort |
aggregation and fibril morphology of the arctic mutation of alzheimer's aβ peptide by cd, tem, stem and in situ afm |
publishDate |
2012 |
url |
https://openrepository.ru/article?id=177121 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
SCOPUS10478477-2012-180-1-SID84866988080 |
op_relation |
Journal of Structural Biology 1 180 174 http://rour.neicon.ru:80/xmlui/bitstream/rour/177121/1/nora.pdf 1047-8477 https://openrepository.ru/article?id=177121 |
_version_ |
1766328945038327808 |