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 type Alzheimer’...
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ftpubmed:oai:pubmedcentral.nih.gov:3466396 2023-05-15T15:00:29+02:00 Aggregation and Fibril Morphology of the Arctic Mutation of Alzheimer’s Aβ peptide by CD, TEM, STEM and in situ AFM Norlin, Nils Hellberg, Magnus Filippov, Andrei Sousa, Alioscka A. Gröbner, Gerhard Leapman, Richard D. Almqvist, Nils Antzutkin, Oleg N. 2012-06-28 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466396 http://www.ncbi.nlm.nih.gov/pubmed/22750418 https://doi.org/10.1016/j.jsb.2012.06.010 en eng http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466396 http://www.ncbi.nlm.nih.gov/pubmed/22750418 http://dx.doi.org/10.1016/j.jsb.2012.06.010 © 2012 Elsevier Inc. All rights reserved. Article Text 2012 ftpubmed https://doi.org/10.1016/j.jsb.2012.06.010 2013-10-06T00:33:52Z 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 ~3 nm 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): ≤2.5 μM and 12.5 μM, respectively. Moreover, at the same concentration, 50 μM, the aggregation process proceeds more rapidly for arc-Aβ(1-40): The first amyloid fibrils were observed after ca 72 hours from the onset of incubation as compared to approximately 7 days 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. Text Arctic PubMed Central (PMC) Arctic Journal of Structural Biology 180 1 174 189 |
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Article Norlin, Nils Hellberg, Magnus Filippov, Andrei Sousa, Alioscka A. Gröbner, Gerhard Leapman, Richard D. Almqvist, Nils Antzutkin, Oleg N. Aggregation and Fibril Morphology of the Arctic Mutation of Alzheimer’s Aβ peptide by CD, TEM, STEM and in situ AFM |
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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 ~3 nm 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): ≤2.5 μM and 12.5 μM, respectively. Moreover, at the same concentration, 50 μM, the aggregation process proceeds more rapidly for arc-Aβ(1-40): The first amyloid fibrils were observed after ca 72 hours from the onset of incubation as compared to approximately 7 days 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. |
format |
Text |
author |
Norlin, Nils Hellberg, Magnus Filippov, Andrei Sousa, Alioscka A. Gröbner, Gerhard Leapman, Richard D. Almqvist, Nils Antzutkin, Oleg N. |
author_facet |
Norlin, Nils Hellberg, Magnus Filippov, Andrei Sousa, Alioscka A. Gröbner, Gerhard Leapman, Richard D. Almqvist, Nils Antzutkin, Oleg N. |
author_sort |
Norlin, Nils |
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 |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466396 http://www.ncbi.nlm.nih.gov/pubmed/22750418 https://doi.org/10.1016/j.jsb.2012.06.010 |
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Arctic |
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Arctic |
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Arctic |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466396 http://www.ncbi.nlm.nih.gov/pubmed/22750418 http://dx.doi.org/10.1016/j.jsb.2012.06.010 |
op_rights |
© 2012 Elsevier Inc. All rights reserved. |
op_doi |
https://doi.org/10.1016/j.jsb.2012.06.010 |
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Journal of Structural Biology |
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180 |
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1 |
container_start_page |
174 |
op_container_end_page |
189 |
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1766332583862337536 |