ArticleJournal of the American Chemical Society2015
N-Terminal Extensions Retard Aβ42 Fibril Formation but Allow Cross-Seeding and Coaggregation with Aβ42.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Clinically relevant stereochemistry reprograms amyloid proteome for aggregation cross-talk-conferred neuroprotection.Science advances · 2026Article
- General integrated rate law for complex self-assembly reactions reveals the mechanism of amyloid-beta coaggregation.Physical chemistry chemical physics : PCCP · 2025Article
- Secondary nucleation as a strategy towards hierarchically organized mesoscale topologies in supramolecular polymerization.Nature chemistry · 2025Review
- Accelerated Alzheimer's Aβ-42 secondary nucleation chronologically visualized on fibril surfaces.Science advances · 2024Article
- Hydroxytyrosol-Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer's Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells.International journal of molecular sciences · 2023Article
- Single-molecule visualization determines conformational substate ensembles in β-sheet-rich peptide fibrils.Science advances · 2023Article
- Direct observation of secondary nucleation along the fibril surface of the amyloidProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of Hydrophobicity at the N-Terminal Region of Aβ42 in Secondary Nucleation.ACS chemical neuroscience · 2022Article
- Amyloid Cross-Seeding: Mechanism, Implication, and Inhibition.Molecules (Basel, Switzerland) · 2022Review
- Amyloid-β peptide 37, 38 and 40 individually and cooperatively inhibit amyloid-β 42 aggregation.Chemical science · 2022Article
- Proliferation of Tau 304-380 Fragment Aggregates through Autocatalytic Secondary Nucleation.ACS chemical neuroscience · 2021Article
- Expression of N-Terminal Cysteine AβBiochemistry · 2021Article
- The role of fibril structure and surface hydrophobicity in secondary nucleation of amyloid fibrils.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Toxicity and Polymorphism of β-Amyloid Oligomers.International journal of molecular sciences · 2020Review
- Small molecule-mediated co-assembly of amyloid-β oligomers reduces neurotoxicity through promoting non-fibrillar aggregation.Chemical science · 2020Article
- Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aβ42 peptide.Nature chemistry · 2020Article
- Rapid, Refined, and Robust Method for Expression, Purification, and Characterization of Recombinant Human Amyloid beta 1-42.Methods and protocols · 2019Article
- Identification of neurotoxic cross-linked amyloid-β dimers in the Alzheimer's brain.Brain : a journal of neurology · 2019Article
- Modular genetic design of multi-domain functional amyloids: insights into self-assembly and functional properties.Chemical science · 2019Article
- A method of predicting the in vitro fibril formation propensity of Aβ40 mutants based on their inclusion body levels in E. coli.Scientific reports · 2019Article
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Amyloid β-protein (Aβ) sequence length variants with varying aggregation propensity coexist in vivo, where coaggregation and cross-catalysis phenomena may affect the aggregation process. Until recently, naturally occurring amyloid β-protein (Aβ) variants were believed to begin at or after the canonical β-secretase cleavage site within the amyloid β-protein precursor. However, N-terminally extended forms of Aβ (NTE-Aβ) were recently discovered and may contribute to Alzheimer's disease. Here, we have used thioflavin T fluorescence to study the aggregation kinetics of Aβ42 variants with N-terminal extensions of 5-40 residues, and transmission electron microscopy to analyze the end states. We find that all variants form amyloid fibrils of similar morphology as Aβ42, but the half-time of aggregation (t1/2) increases exponentially with extension length. Monte Carlo simulations of model peptides suggest that the retardation is due to an underlying general physicochemical effect involving reduced frequency of productive molecular encounters. Indeed, global kinetic analyses reveal that NTE-Aβ42s form fibrils via the same mechanism as Aβ42, but all microscopic rate constants (primary and secondary nucleation, elongation) are reduced for the N-terminally extended variants. Still, Aβ42 and NTE-Aβ42 coaggregate to form mixed fibrils and fibrils of either Aβ42 or NTE-Aβ42 catalyze aggregation of all monomers. NTE-Aβ42 monomers display reduced aggregation rate with all kinds of seeds implying that extended termini interfere with the ability of monomers to nucleate or elongate. Cross-seeding or coaggregation may therefore represent an important contribution in the in vivo formation of assemblies believed to be important in disease.
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