Alzheimer’s disease is a neurodegenerative disorder characterized by deposits of misfolded proteins in the brain. The peptide amyloid-ꞵ42 (Aꞵ-42) is found to form into oligomeric structures, and have been discovered to have the most neurotoxic properties. Micelle structures such as sodium-dodecyl sulfate (SDS) have been shown to stabilize the formation of Aꞵ-42 oligomers, which can be used for further study of the these structures. Molecular dynamic simulations have shown that the hydrophobic pockets at position 33 and 37 of the Aꞵ42 peptide can interact with the hydrocarbon tails of the micelles, which can further stabilize the oligomers. To investigate this property, the glycine residues at these positions were substituted with a more hydrophobic residue - valine - to mimic the hydrocarbon tail. It is hypothesized that these substitutions of the peptide (labeled G33V and G37V) will be prone to oligomer formation without the need for a detergent-assisted pathway. Size-exclusion chromatography, Thioflavin-T fluorescence assays, and other analytical techniques have shown that G33V and G37V have a higher tendency to form oligomeric structures than the wild-type Aꞵ-42. These properties have led to more insight about the pathway of oligomerization, and more clarity about the properties of Aꞵ-42. These discoveries are the basis for experiments such as 2D nuclear magnetic resonance spectroscopy (2D-NMR), as well as cellular experiments for organismic reactions to Aꞵ-42 oligomers. Future experiments will allow for discovery into these pathways and the potential development of therapeutics for Alzheimer’s disease.
