کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5914575 | 1162743 | 2012 | 16 صفحه PDF | دانلود رایگان |
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 â¼3 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.
AFM images of polymorphs of amyloid fibrils of the wild type and the Arctic mutation Alzheimer's Aβ(1-40).89
Journal: Journal of Structural Biology - Volume 180, Issue 1, October 2012, Pages 174-189