Amyloid-forming proteins undergo a structural transition from alpha-helical to disordered conformations and, ultimately, cross-beta fibrils. The unfolding and aggregation of the amyloid beta-peptide (A beta) have been implicated in the development and progression of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). However, the events underlying the initial structural transition leading to the disease state remain unclear. Although most cases are sporadic, several genetic variants exist that alter the electrostatic properties of A beta and lead to more rapid unfolding and more severe phenotypes. In the present study, the enhanced unfolding is shown to be due to the mutated side chains altering the local peptide-bond dipole moments leading to local destabilization of the alpha-helix, as determined from polarizable molecular dynamics (MD) simulations of wild-type (WT) A beta fragments and several common mutations. The local perturbation of the helix then leads to progressive unwinding of the alpha-helix in a cooperative fashion due to decreases in adjacent (i +/- 1) and hydrogen-bonded (i + 4) peptide-bond dipole moments. Side-chain dynamics, subsequent variations in dipole moments, and ultimately the response in the peptide-bond dipole moments are all modulated by solvent dielectric properties based on simulations in water versus ethanol. The polarizable simulation results, along with simulations using the additive CHARMM36 force field, further indicate that cooperativity due to the alignment of peptide bonds leading to enhanced dipole moments is a fundamental force in stabilizing alpha-helices.