Aβ Peptide Fibril Formation and Its Implications for Alzheimer's Disease
Author Information
Author(s): Kristoffer Brännström, Anders Öhman, Anders Olofsson
Primary Institution: Umeå University
Hypothesis
The architecture of Aβ fibrils is determined by constraints imposed by the monomer conformation during docking and isomerisation.
Conclusion
The study shows that the kinetic rate of fibril formation, rather than the thermodynamically lowest energy state, determines the overall fibrillar structure.
Supporting Evidence
- Aβ fibril extension follows a template guided 'dock and lock' mechanism.
- The kinetic rate of fibril formation determines the fibrillar architecture.
- Aβ40WT has a restricted ability to dock and isomerise with high binding affinity onto Aβ40Arc fibrils.
Takeaway
This study looks at how a protein related to Alzheimer's disease forms structures in the brain, showing that how quickly these structures form is more important than their energy stability.
Methodology
The study used surface plasmon resonance (SPR) and quenched hydrogen-deuterium exchange NMR to analyze the fibrillar structure and polymerisation properties of Aβ peptides.
Potential Biases
Potential bias due to the authors' affiliations and funding sources.
Limitations
The study does not determine if the impaired incorporation of Aβ40WT into Aβ40Arc fibrils is due to structural limitations of the monomer or interactions with the fibril end.
Digital Object Identifier (DOI)
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