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Aβ40 and Aβ42 make separate fibrils after mixed nuclei
In mixtures, Aβ42 fibrillizes first; elongation and secondary nucleation stay homospecific, so each peptide builds its own fibrils.
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Where do Aβ40 and Aβ42 strongly interact?
At primary nucleation; mixed species only among the smallest aggregates.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
What do elongation and secondary nucleation produce?
Distinct homomolecular Aβ42 or Aβ40 fibrils.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
When are two kinetic transitions seen?
At low total concentration, below about 10 μM.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
Which peptide forms the first fibrils?
Aβ42; first-plateau fibrils contain <13% Aβ40.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
How was each transition assigned?
Isotope labels plus trypsin digestion MS of remaining monomers.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
What do NMR monomer-depletion traces show?
Aβ42 drops hours before Aβ40 in 1:1 mixtures.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
Cryo-TEM helical half-pitches?
162 ± 21 nm (Aβ40) vs 31 ± 17 nm (Aβ42).
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
Does Aβ42 monomer accelerate Aβ40?
Yes, but Aβ42 fibrils do not—cooperation is at primary nucleation.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
How do self- vs cross-seeds compare?
Self-seeding is strong even at 0.5–10% seed; Aβ40 seeds poorly catalyze Aβ42.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
What does a 1:1 mixture ThT curve look like vs pure peptides?
Two distinct transitions instead of one sigmoid.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified
Why is primary nucleation least discriminative?
Primary nuclei/small oligomers have the least structural organization.
Source: The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation · DOI · quote verified