1) Amyloid hexapeptide molecules are effective in the treatment of the murine model of neuroinflammation, known as experimental autoimmune encephalomyelitis (EAE). However, in collaboration with the Steinman group at Stanford, we found that the efficacy of such treatments differs between two inbred mouse strains, C57BL/6J (B6) and C57BL/10SnJ (B10). We found that amyloid hexapeptide treatments improved the clinical outcomes of B6, but not B10 mice, indicating that genetic background influences therapeutic efficacy. Moreover, although previous studies indicated that prion protein deficiency results in more severe EAE in B6 mice, we observed no such effect in B10 mice. In addition, we found that amyloid hexapeptide treatments of B10 and B6 mice elicited differential IL4 responses. Thus, the modulatory potential of prion protein and related treatments with other amyloid hexpeptides in EAE depends on mouse strain. 2) There is now substantial evidence that soluble oligomers are primary toxic agents in amyloid diseases. The development of an antibody recognizing the toxic soluble oligomeric forms of different and unrelated amyloid species suggests a common conformational intermediate during amyloidogenesis. The Daggett lab at the University of Washington previously observed a common occurrence of a novel secondary structure element, which they call alpha-sheet, in molecular dynamics (MD) simulations of various amyloidogenic proteins. They hypothesized that the toxic conformer is composed of alpha-sheet structure. As such, alpha-sheet may represent a conformational signature of the misfolded intermediates of amyloidogenesis and a potential unique binding target for peptide inhibitors. Recently, we helped the Daggett lab characterize a novel hairpin peptide (1 or AP90) that adopts stable alpha-sheet structure and inhibits the aggregation of the beta-Amyloid Peptide A42 and transthyretin. AP90 is a 23-residue hairpin peptide featuring alternating D- and L-amino acids with favorable conformational propensities for alpha-sheet formation, and a designed turn. For this study, they reverse engineered AP90 to identify which of its design features is most responsible for conferring alpha-sheet stability and inhibitory activity. We helped them experimentally characterize (FTIR) of seven peptides designed to accomplish this. In addition, they measured the peptides' ability to inhibit aggregation in three unrelated amyloid species: A42, transthyretin, and human islet amylin polypeptide. We found that a hairpin peptide featuring alternating L- and D-amino acids, independent of sequence, is sufficient for conferring alpha-sheet structure and inhibition of aggregation. Additionally, we show a correlation between alpha-sheet structural stability and inhibitory activity.