Chemical biology
Aβ40 and Aβ42 make separate fibrils after mixed nuclei
Open access · cc by · source: Europe PMC
In mixtures, Aβ42 fibrillizes first; elongation and secondary nucleation stay homospecific, so each peptide builds its own fibrils.
How this study connects
Role on claims
Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.
Mechanism papers use NMR as one reporter among several. ¹³C NMR plus crystallography showed how crotonaldehyde inactivates DERA via K167 and C47; isotope-resolved NMR with ThT and cryo-TEM showed Aβ40 and Aβ42 forming separate homomolecular fibrils after mixed nucleation; ¹H NMR Ka ≈ 75 558 M⁻¹ for DMA binding tracked allosteric opening of a Pt tweezer catalyst.
Evidence for the claim as stated.
Cryo-TEM pitch can distinguish two amyloid polymorphs that mixed nucleation might have been expected to scramble. Aβ40 fibrils have a helical half-pitch of 162 nm versus 31 nm for Aβ42; first fibrils are Aβ42 (<13% Aβ40). Cross-seeding is weak versus self-seeding. Atomic mixed-oligomer structures are not solved.
Evidence for the claim as stated.
Discoveries this paper informs or conflicts with
- Two amyloid peptides share a solution, form separate fibrils, and still affect each other
This paper informs this development.
Study at a glance
- Design
- Animal / in-vitro — ThT, CD, isotope-resolved MS/NMR, cryo-TEM, and self- versus cross-seeding of Aβ40/Aβ42 mixtures
- N
- Kinetic and structural assays on 10^14–10^15 monomers per sample
- Population
- Binary mixtures of synthetic Aβ40 and Aβ42 peptides
- Outcome
- Aβ40 and Aβ42 form separate homomolecular fibrils; they cross-react mainly during primary nucleation
Structured fields used in claim comparison tables when every cited study has a complete layer.
Inspect source passages
Aβ40 and Aβ42 make separate fibrils after mixed nuclei
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Less than 13% of Aβ40 is in fibrils at the first plateau.
From the small peaks and level of noise at the position where the Aβ40 signal should appear, we can deduce that less than 13% of Aβ40 is contained in the fibrils at this stage.
Helical half-pitch was 162 ± 21 nm for Aβ40 and 31 ± 17 nm for Aβ42.
The measurement of the typical helical half pitch (node-to-node distance) was performed using grey scale profiles () and was found to be 162 ± 21 nm for Aβ40 and 31 ± 17 nm for Aβ42, .
Key findings
Two transitions below ~10 μM; first fibrils are Aβ42 (<13% Aβ40). Helical half-pitch 162 nm (Aβ40) vs 31 nm (Aβ42). Cross-seeding is weak versus self-seeding; Aβ42 monomers accelerate Aβ40 primary nucleation.
Methodology
Authors combined ThT, CD, isotope-resolved MS/NMR, cryo-TEM pitch measurements and self- vs cross-seeding to dissect microscopic steps in Aβ40:Aβ42 mixtures.
Limitations
Atomic mixed-oligomer structures are not solved; disease relevance is inferred from peptide biophysics, not patients.
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