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.
Source
The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation
What they did
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.
What they found
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.
The limits
What it doesn't show
Atomic mixed-oligomer structures are not solved; disease relevance is inferred from peptide biophysics, not patients.
Key terms
- Primary nucleation
- Formation of the first aggregates from monomers; the least sequence-specific step here.
- Secondary nucleation
- Surface-catalyzed formation of new fibrils on existing fibrils; highly homospecific.
- Homomolecular fibril
- Fibril built from only Aβ40 or only Aβ42, not a statistical copolymer.
- Thioflavin T (ThT)
- Dye whose fluorescence reports β-sheet amyloid.
- Cross-seeding
- Using fibrils of one peptide to nucleate the other.
Flashcards
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Quiz yourself
Fibrils in Aβ40/Aβ42 mixtures are:
Common questions
Do mixed fibrils form?
Not detectably; fibrils are homomolecular.
Where do the peptides mix?
At primary nucleation/small oligomers.
Which peptide aggregates first?
Aβ42, then Aβ40.
How do TEM pitches differ?
~162 nm (Aβ40) vs ~31 nm (Aβ42).
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