Recent studies from a joint collaboration between our group and the Dietler laboratory at the EPFL provide, for the first time, direct evidence that Aβ42 fibrillization occurs via a combined mechanism of nucleated polymerization and secondary nucleation (see Jeong et al., 2013).
However, our AFM studies demonstrated that secondary nucleation occurs on the surface of only specific types of Aβ fibrils. For example, in the case of Aβ42, only "type 2" fibrils appear to be capable of growing via secondary nucleation events.
We did not investigate the generation of oligomers as a result of secondary nucleation events on the surface of fibrils, but the data provided by Knowles and colleagues provide strong evidence that this is possible.
It would be interesting to determine how the structural morphology of the parent fibrils influences the frequency and rate of secondary nucleation and what molecular factors and/or cellular events may influence this process.
More importantly, the results presented by Knowles and colleagues provide very nice mechanistic explanations for...