P013 - THE RELATIONSHIP BETWEEN THE PATH OF AMYLOID-Β FIBRIL FORMATION AND THEIR PROPERTIES.
Abstract
Aims
The aim of this study is to investigate how Aβ1–40 and Aβ1–42 isoforms interact to better understand how pathological fibril formation occurs in vivo.
Methods
To learn the cross-incorporation of Aβ1–40 and Aβ1–42 monomeric peptides onto the fibrillar forms of Aβ1–40 and Aβ1–42 respectively, we performed cross-templating experiments using Surface plasmon resonance (SPR)-assay.
To learn cross-nucleation between Aβ1–40 and Aβ1–42 in solution and the properties of cross-nucleated fibrils, we performed Thiaflavin-T (ThT-assay) that followed SPR assay.
Results
SPR-assay indicates that Aβ1-42 monomers are easily incorporated onto the fibrillar form of Aβ1-40 and they also acquire the properties of Aβ1-40. On the other hand, Aβ1-40 monomers are inhibited from incorporating onto the fibrillar form Aβ1-42. ThT assay indicates that fibrils derived via SCSN do not acquire the properties of the parental fibrils.
Conclusions
In conclusion, there is an intrinsic barrier that prevents a more abundant Aβ1–40 variant from adopting the fibrillar properties of more cytotoxic Aβ1–42. Also, the path of fibril formation controls the transfer of fibrillar properties between amyloid-β fibrils.
