(534a) Hofmeister Effects on Aggregation and Prion Strain Generation By Amyloid Beta 1-42

Aggregation of amyloid-beta peptides to form plaques is a key event in the pathogenesis of Alzheimer’s disease (AD). Amyloid beta_1-42 is one of the most abundant species in amyloid plaques and is considered to play a central role in pathogenesis of AD. It has been shown to aggregate in vitro like many other amyloid proteins, however, the effect of environmental factors on aggregation of Amyloid beta_1-42 has not been investigated systematically. In this work we have studied the effect of ions on the aggregation of Amyloid beta_1-42. Previous work from our group on amyloid formation by Sup35NM protein containing the prion domain of yeast prion protein Sup35p has shown that strongly hydrated anions (kosmotropes) initiate nucleation quickly and cause rapid fiber elongation, whereas poorly hydrated anions (chaotropes) delay nucleation and reduce the elongation rate. The Hofmeister salts also determined the amyloid strain that was preferentially formed with strong strains being formed in kosmotropes and weak strains in chaotropes. Here, we have investigated how Hofmeister ions affect the aggregation kinetics of Amyloid beta_1-42 peptide. Preliminary results indicate that aggregation behavior of Amyloid beta_1-42 in the presence of Hofmeister salts, particularly the highly chaotropic perchlorate, is widely different from Sup35NM which suggests that these proteins may aggregate by different mechanisms. Further, the biophysical properties of the amyloid strains formed by Amyloid beta_1-42 in the presence of Hofmeister salts will also be studied to gain insights into the aggregation mechanism of Amyloid beta_1-42.

 [1] Jonathan Rubin, Hasan Khosravi, Kathryn L. Bruce, Megan E. Lydon, Sven H. Behrens, Yury O. Chernoff, Andreas S. Bommarius.(2013), Ion-Specific Effects on Prion Nucleation and Strain Formation. J. Biol. Chem.18; 288(42):30300-8 doi: 10.1074/jbc.M113.467829

[2] Yeh, V., Broering, J. M., Romanyuk, A., Chen, B., Chernoff, Y. O. and Bommarius, A. S. (2010), The Hofmeister effect on amyloid formation using yeast prion protein. Protein Science, 19: 47–56. doi: 10.1002/pro.281

[3] Aditi Sharma, Kathryn L. Bruce, Buxin Chen, Stefka Gyoneva, Sven H. Behrens, Andreas S. Bommarius, Yury O. Chernoff. Role of the environment of cross-seeding reaction in the prion species barrier. J. Biol. Chem. To be submitted.