Aβ42 fibril formation from predominantly oligomeric samples suggests a link between oligomer heterogeneity and fibril polymorphism.
TL;DR: It is shown that Aβ42 spontaneously forms oligomers with a wide range of sizes in the same sample, and results suggest that the fibrils formed by larger oligomers may adopt a different structure from fibrILS formed by smaller oligomers, pointing to a link between oligomer heterogeneity and fibril polymorphism.
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Abstract: Amyloid-β (Aβ) oligomers play a central role in the pathogenesis of Alzheimer's disease. Oligomers of different sizes, morphology and structures have been reported in both in vivo and in vitro studies, but there is a general lack of understanding about where to place these oligomers in the overall process of Aβ aggregation and fibrillization. Here, we show that Aβ42 spontaneously forms oligomers with a wide range of sizes in the same sample. These Aβ42 samples contain predominantly oligomers, and they quickly form fibrils upon incubation at 37°C. When fractionated using ultrafiltration filters, the samples enriched with smaller oligomers form fibrils at a faster rate than the samples enriched with larger oligomers, with both a shorter lag time and faster fibril growth rate. This observation is independent of Aβ42 batches and hexafluoroisopropanol treatment. Furthermore, the fibrils formed by the samples enriched with larger oligomers are more readily solubilized by epigallocatechin gallate, a main catechin component of green tea. These results suggest that the fibrils formed by larger oligomers may adopt a different structure from fibrils formed by smaller oligomers, pointing to a link between oligomer heterogeneity and fibril polymorphism.
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Citations
Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimer's disease
Jay Rasmussen,Jay Rasmussen,Jasmin Mahler,Natalie Beschorner,Stephan A. Kaeser,Stephan A. Kaeser,Lisa M. Häsler,Lisa M. Häsler,Frank Baumann,Frank Baumann,Sofie Nyström,Erik Portelius,Erik Portelius,Kaj Blennow,Kaj Blennow,Tammaryn Lashley,Nick C. Fox,Diego Sepulveda-Falla,Diego Sepulveda-Falla,Markus Glatzel,Adrian L. Oblak,Bernardino Ghetti,K. Peter R. Nilsson,Per Hammarström,Matthias Staufenbiel,Lary C. Walker,Mathias Jucker,Mathias Jucker +27 more
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TL;DR: In this paper, the spectral properties of conjugated oligothiophenes (LCO) were analyzed for β-amyloid plaques in postmortem tissue sections from frontal, temporal, and occipital neocortices in 40 cases of familial Alzheimer's disease (AD) or sporadic (idiopathic) AD (sAD).
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The Role of Lipid Environment in Ganglioside GM1-Induced Amyloid β Aggregation.
Vladimir Rudajev,Jiri Novotny +1 more
- 09 Sep 2020
TL;DR: GM1 has been shown to induce specific changes in the spatial organization of Aβ, which lead to enhanced peptide accumulation and deleterious effect especially on neuronal membranes containing clusters of this ganglioside.
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Aβ42 fibril formation from predominantly oligomeric samples suggests a link between oligomer heterogeneity and fibril polymorphism.
TL;DR: It is shown that Aβ42 spontaneously forms oligomers with a wide range of sizes in the same sample, and results suggest that the fibrils formed by larger oligomers may adopt a different structure from fibrILS formed by smaller oligomers, pointing to a link between oligomer heterogeneity and fibril polymorphism.
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TL;DR: In this paper, a review explores factors contributing to the lack of consistency in experimental approaches taken to model Aβ aggregation and toxicity, and provides an overview of the different techniques available to analyse Aβ, such as electron and atomic force microscopy, nuclear magnetic resonance spectroscopy, dye-based assays, size exclusion chromatography, mass spectrometry, and SDS-PAGE.
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Molecular Chaperones’ Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis
Sumit Kinger,Ankur Rakesh Dubey,Prashant Kumar,Y. A. Jagtap,Akash Choudhary,Anil Kumar,Vijay Kumar Prajapati,Rohan Dhiman,Amit Misra +8 more
TL;DR: In this article , the authors discuss how the HSP70 and DNAJ family co-chaperones can act as potential targets for reducing misfolded protein accumulation in ALS, and how small HSPB1 and HSPb8 chaperones facilitate neuroprotection and prevent stress-associated misfolding protein apoptosis. But the lack of a thorough understanding of chaperone involvement in ALS pathogenesis presents a significant challenge in its treatment.
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