Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFMShow others and affiliations
2012 (English)In: Journal of Structural Biology, ISSN 1047-8477, E-ISSN 1095-8657, Vol. 180, no 1, p. 174-189Article in journal (Refereed) Published
Abstract [en]
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 c.a. 72 h 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.
Place, publisher, year, edition, pages
2012. Vol. 180, no 1, p. 174-189
National Category
Other Physics Topics Physical Chemistry
Research subject
Experimental Physics; Chemistry of Interfaces
Identifiers
URN: urn:nbn:se:ltu:diva-12848DOI: 10.1016/j.jsb.2012.06.010ISI: 000310046400020PubMedID: 22750418Scopus ID: 2-s2.0-84866988080Local ID: bfea934d-f775-415b-8e89-4ba68ada9687OAI: oai:DiVA.org:ltu-12848DiVA, id: diva2:985799
Note
Validerad; 2012; 20120806 (ysko)
2016-09-292016-09-292023-09-05Bibliographically approved