Ulf Olsson

The Aβ42 peptide (APP(672–713)), associated with Alzheimer disease, is highly prone to form amyloid fibrils and has been extensively studied through in vitro experiments. Such experiments represent a basis for understanding the biophysical chemistry of amyloid-related diseases. In this communication, we show that homogeneous primary nucleation in vitro of Aβ42 fibrils is a very rare event, implying that primary nucleation occurs almost exclusively at interfaces, by heterogeneous nucleation. Recognizing that the protein molecules in amyloid fibrils possess a two-dimensional fold, we discuss the nucleation in relation to protein folding and Levinthal's paradox. In the much more rapid heterogeneous nucleation, we suggest that one catalyzing effect is the significant reduction of the effective conformational space when a monomer polypeptide chain (strongly) adsorbs to a surface, facilitating its search for the target fold.