3. Conclusions
The Aβ42 monomer and oligomer structures in aqueous solution are of high importance as they initiate fibril formation and are believed to be the most toxic species. While the community believes on random coil – β-sheet oligomers and the role of β-hairpin82 in the early steps of aggregation, the existence of α-helical bundle metastable intermediates of Aβ42 oligomers is rarely cited, while it is predicted by AlphaFold2 and is, more importantly, supported indirectly by a large number of experimental studies on Aβ and many amyloid polypeptides under various conditions. It is important to note that there is a general resistance of the field to believing CD in detecting α-helix in aggregates, because of light-scattering interference and skewing of the CD spectrum.  But the α-helix signal in oligomers was further evidenced by FTIR and Raman spectroscopies in addition to CD.  Clearly, the coexistence of α-rich oligomers and β-rich oligomers en route to fibril formation has to be considered when designing drugs targeting Aβ monomers and oligomers.76,81,83,84
AUTHOR INFORMATION
Corresponding Author
E-mail: philippe.derreumaux@ibpc.fr
ORCID:
Derreumaux: 0000-0001-9110-5585
Sterpone: 0000-0003-0894-8069, fabio.sterpone@ibpc.fr
Nguyen: 0000-0003-1284-967X, Phuong.nguyen@ibpc.fr
Notes. The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the “Initiative d’Excellence” program from the French State, Grant “DYNAMO”, ANR-11-LABX-0011. PD thanks Ronald Wetzel for useful discussions and Geoffrey Letessier of the Laboratoire de Biochimie Théorique for technical support.