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.
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.
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.
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