Stabilizing Highly Pathogenic Nanoparticles Associated with Alzheimer’s Disease

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When the Aß peptides aggregate into soluble oligomeric clusters, they form central nervous system neurotoxins known as amyloid-ß-derived diffusible ligands (ADDLs). The assembly of ADDLs is currently thought to be a pathogenic process in Alzheimer's disease (AD). Understanding the molecular structure and properties of ADDLs could prove useful in the design of treatments. Because ADDLs easily denature, it is difficult to isolate them for study using classical methods such as gel electrophoresis or SDS-PAGE. This research developed a technique for isolating intact ADDLs oligomers. Using photo-induced cross-linking of unmodified proteins (PICUP) enabled the formation of covalent bonds between Aß polypeptide chains to stabilize the ADDLs. The strength of the cross-linked ADDLs was tested through SDS-PAGE. The surface of the proteins was mapped with atomic force microscopy (AFM) to confirm that the PICUP process did not alter the shape of the oligomers. This work also demonstrated that the PICUP method stabilizes ADDLs without altering their innate properties.

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  • 07/19/2018
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