Mutations within the β-amyloid peptide (Aβ) sequence that cause early onset familial Alzheimer's disease (FAD) have been shown to promote Aβ aggregation. How these FAD-related mutants increase the aggregative ability of Aβ is not fully understood. Here, we characterized the effect of the Arctic variant (E22G) on the conformational stability of Aβ using various forms of spectroscopy and kinetic analyses, including nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM). The E22G mutation in the Arctic variant reduced the α-helical propensity and conformational stability of Aβ on residues 15-25. This mutation also caused an increase in both α-helix-to-β-strand conversion and fibril nucleation rates. Our results suggest that the α-helical propensity of residues 15-25 may play a determinant role in the aggregative ability of Aβ. This may provide a structural basis for understanding the molecular mechanism of Aβ aggregation.