Amyloid-beta (Aβ) peptides play a key role in the pathology of Alzheimer’s disease. Although naturally occurring, excessive nucleation and aggregation of Aβ peptides can lead to the formation of plaque deposits in the cerebrospinal fluid and around neuronal cells, which contributes to neurodegeneration. Previous studies have shown various behaviors of Aβ due to post-translational modifications (PTMs) on a select number of amino acid residues. The site-specific nature of Aβ, however, makes it difficult to generalize the effects of each PTM on the aggregation of these peptides. This study investigates the effects of peptide modifications -  specifically phosphorylation, pyroglutamylation, and isomerization - on Aβ fibril formation. The aggregation rate of wild-type (WT) Aβ parent fibrils seeded with solutions of sonicated Aβ modified peptides was monitored utilizing a thioflavin-T (ThT) kinetic fluorescence assay. ThT, a benzothiazole salt, exhibits enhanced fluorescence when bound to beta sheet-rich structures in solution, structures which result from the aggregation of Aβ peptides. The preliminary kinetic detection assay results of the WT Aβ parent fibril solutions seeded with the sonicated modified peptide solutions showed a change in lag phases, as well as an overall lower ThT fluorescence intensity as compared to the WT Aβ parent fibril solutions seeded with sonicated WT Aβ peptides.  The preliminary results suggest post-translational modifications of Aβ peptides modified the rate at which the peptides aggregate to form amyloid plaques.  This fundamental understanding of Aβ plaque formation can aid in future therapeutic design.

Monitoring the effects of post-translational modifications on amyloid-beta peptide aggregation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.