ArticleProceedings of the National Academy of Sciences of the United States of America2020
Ultrastructural evidence for self-replication of Alzheimer-associated Aβ42 amyloid along the sides of fibrils.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 58 citations in OpenAlex.
- Mechanism-selective inhibition of α-synuclein aggregation by the chaperone-like BRICHOS domain.The Journal of biological chemistry · 2026Article
- The chaperone DNAJB6b halts amyloid formation through association with transient Aβ oligomers.Physical chemistry chemical physics : PCCP · 2026Article
- Zooming into Disease at the Nanoscale: High-Speed Atomic Force Microscopy in Biomedical Discovery.ACS nano · 2026Review
- Does amyloid fibril nucleation occur at surfaces only?Biophysical journal · 2026Article
- Aducanumab binding to AβProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aducanumab Binding to AβbioRxiv : the preprint server for biology · 2025Article
- General integrated rate law for complex self-assembly reactions reveals the mechanism of amyloid-beta coaggregation.Physical chemistry chemical physics : PCCP · 2025Article
- Direct Observation of Secondary Nucleation in Huntingtin Amyloid Formation by High-Speed Atomic Force Microscopy.Journal of the American Chemical Society · 2025Article
- Article
- The role of shear forces in primary and secondary nucleation of amyloid fibrils.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Evaluating the inter-species transmission risk of amyloid beta peptide aggregates via ingestion.Alzheimer's research & therapy · 2024Article
- The supersaturation perspective on the amyloid hypothesis.Chemical science · 2023Review
- Molecular modeling of apoE in complexes with Alzheimer's amyloid-β fibrils from human brain suggests a structural basis for apolipoprotein co-deposition with amyloids.Cellular and molecular life sciences : CMLS · 2023Article
- The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain.Nature communications · 2023Article
- Role of conformational dynamics in pathogenic protein aggregation.Current opinion in chemical biology · 2023Review
- ERp57 chaperon protein protects neuronal cells from Aβ-induced toxicity.Journal of neurochemistry · 2022Article
- Aggregation Behavior of Structurally Similar Therapeutic Peptides Investigated byMolecular pharmaceutics · 2022Article
- The N-Terminal Domain of AβThe journal of physical chemistry. B · 2022Article
- Amyloid β 42 fibril structure based on small-angle scattering.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Challenges in sample preparation and structure determination of amyloids by cryo-EM.The Journal of biological chemistry · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nucleation of Alzheimer-associated Aβ peptide monomers can be catalyzed by preexisting Aβ fibrils. This leads to autocatalytic amplification of aggregate mass and underlies self-replication and generation of toxic oligomers associated with several neurodegenerative diseases. However, the nature of the interactions between the monomeric species and the fibrils during this key process, and indeed the ultrastructural localization of the interaction sites have remained elusive. Here we used NMR and optical spectroscopy to identify conditions that enable the capture of transient species during the aggregation and secondary nucleation of the Aβ42 peptide. Cryo-electron microscopy (cryo-EM) images show that new aggregates protrude from the entire length of the progenitor fibril. These protrusions are morphologically distinct from the well-ordered fibrils dominating at the end of the aggregation process. The data provide direct evidence that self-replication through secondary nucleation occurs along the sides of fibrils, which become heavily decorated under the current solution conditions (14 µM Aβ42, 20 mM sodium phosphate, 200 µM EDTA, pH 6.8).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.