**5. Conclusions**

In the present study, we characterized the effects of E22Q and L17A/F19A mutations on the structural propensities of wild-type Aβ<sup>40</sup> and Aβ40(E22Q), respectively, by CD and NMR spectroscopy. We found that the E22Q mutation has no significant effect on the structural propensity of wild-type Aβ40, indicating that it does not promote aggregation by altering the α-helical propensity of the α/β-discordant region. This finding supported the view that it is not necessary for FAD-related mutations in the α/β-discordant region to promote aggregation by altering the structural propensity of Aβ. Besides wild-type and Arctic-type Aβ40, the L17A/F19A mutation would increase the α-helical propensity of the α/β-discordant region of Dutch-type Aβ40, resulting in inhibition of Aβ40(E22Q) aggregation. It is possible that the L17A/F19A mutation can be applied to inhibit Aβ aggregation in vivo. This study provides the information for a clearer understanding of how mutations within the α/β-discordant region of Aβ affect aggregation.

**Author Contributions:** Conceptualization, K.-C.H., H.-B.H., and T.-H.L.; Data curation, K.-C.H., Y.-R.C., S.-J.H., and C.-Y.T.; Formal analysis, K.-C.H., Y.-R.C., C.-T.L., S.-J.H., and C.-Y.T.; Investigation, K.-C.H., Y.-R.C., S.-J.H., and C.-Y.T.; Methodology, K.-C.H., C.-F.C., S.-J.H., H.-B.H., and T.-H.L.; Project administration, H.-B.H. and T.-H.L.; Software, C.-F.C. and S.-J.H.; Validation, K.-C.H., C.-T.L., and S.-J.H.; Visualization, K.-C.H.; Writing—original draft, K.-C.H.; Writing—review & editing, H.-B.H. and T.-H.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** This work was supported by grants from the Ministry of Science and Technology, ROC (MOST 106-2113-M-010-003, MOST 107-2113-M-010-004, MOST 108-2113-M-010-003) and from Taipei Veterans General Hospital, Taiwan, ROC (V106C-052, V107C-051 and V108C-023) The NMR spectra were obtained at the High-Field NMR Center at Academia Sinica, Instrumentation Center, National Taiwan University and Taipei Veterans General Hospital.

**Conflicts of Interest:** The authors declare no conflicts of interest.
