Amyloid-β Peptide Induces Prion Protein Amyloid Formation: Evidence for Its Widespread Amyloidogenic Effect

Transmissible spongiform encephalopathy is associated with misfolding of prion protein (PrP) into an amyloid beta-rich aggregate. Previous studies have indicated that PrP interacts with Alzheimer's disease amyloid-beta peptide (A beta), but it remains elusive how this interaction impacts on the misfolding of PrP. This study presents the first in vitro evidence that A beta induces PrP-amyloid formation at submicromolar concentrations. Interestingly, systematic mutagenesis of PrP revealed that A beta requires no specific amino acid sequences in PrP, and induces the misfolding of other unrelated proteins (insulin and lysozyme) into amyloid fibrils in a manner analogous to PrP. This unanticipated nonspecific amyloidogenic effect of A beta indicates that this peptide might be involved in widespread protein aggregation, regardless of the amino acid sequences of target proteins, and exacerbate the pathology of many neurodegenerative diseases.