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
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
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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, .
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.
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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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