Secondary Nucleation of Aβ Revealed by Single‐Molecule and Computational Approaches Article Swipe

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N. Helge Meyer , Nicolas Arroyo , Lois Roustan , Jean‐Marc Janot , Saly Charles‐Achille , Joan Torrent , Fabien Picaud , Sébastien Balme ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1002/advs.202404916

Understanding the mechanisms underlying amyloid‐β (Aβ) aggregation is pivotal in the context of Alzheimer's disease. This study aims to elucidate the secondary nucleation process of Aβ42 peptides by combining experimental and computational methods. Using a newly developed nanopipette‐based amyloid seeding and translocation assay, confocal fluorescence spectroscopy, and molecular dynamics simulations, the influence of the seed properties on Aβ aggregation is investigated. Both fragmented and unfragmented seeds played distinct roles in the formation of oligomers, with fragmented seeds facilitating the formation of larger aggregates early in the incubation phase. The results show that secondary nucleation leads to the formation of oligomers of various sizes and structures as well as larger fibrils structured in β‐sheets. From these findings a mechanism of secondary nucleation involving two types of aggregate populations, one released and one growing on the mother fiber is proposed.

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Nucleation Context (archaeology) Chemistry Biophysics Fibril Amyloid (mycology) Molecular dynamics Amyloid fibril Fluorescence Nanotechnology Chemical physics Materials science Biology Computational chemistry Disease Amyloid β Physics Inorganic chemistry Medicine Quantum mechanics Pathology Organic chemistry Paleontology

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Type: article
Language: en
Landing Page: https://doi.org/10.1002/advs.202404916
OA Status: gold
Cited By: 5
References: 50
Related Works: 10
OpenAlex ID: https://openalex.org/W4401694455

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DOI: https://doi.org/10.1002/advs.202404916

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Title: Secondary Nucleation of Aβ Revealed by Single‐Molecule and Computational Approaches

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Language: en

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Publication year: 2024

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Publication date: 2024-08-19

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Authors: N. Helge Meyer, Nicolas Arroyo, Lois Roustan, Jean‐Marc Janot, Saly Charles‐Achille, Joan Torrent, Fabien Picaud, Sébastien Balme

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Landing page: https://doi.org/10.1002/advs.202404916

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Concepts: Nucleation, Context (archaeology), Chemistry, Biophysics, Fibril, Amyloid (mycology), Molecular dynamics, Amyloid fibril, Fluorescence, Nanotechnology, Chemical physics, Materials science, Biology, Computational chemistry, Disease, Amyloid β, Physics, Inorganic chemistry, Medicine, Quantum mechanics, Pathology, Organic chemistry, Paleontology

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Cited by: 5

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Citations by year (recent): 2025: 2, 2024: 3

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References (count): 50

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Related works (count): 10

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publication_date	2024-08-19
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