Conversion between parallel and antiparallel β-sheets in wild-type and Iowa mutant fibrils

Abstract

AbstractUsing a variant of Hamilton-Replica-Exchange we study for wild type and Iowa mutant Aβ40 the conversion between fibrils with antiparallel β-sheets, and such with parallel β-sheets. We show that wild type and mutant form distinct salt bridges that in turn stabilize different fibril organizations. The conversion between the two fibril forms leads to the release of small aggregates that in the Iowa mutant may shift the equilibrium from fibrils to more toxic oligomers.