Studies have found strong correlations between polymorphism and structural variations in amyloid-β (Aβ) fibrils and the diverse clinical subtypes of Alzheimer's disease (AD). Thus, a detailed understanding of the conformational behavior of Aβ fibrils may be an aid to elucidate the pathological mechanisms involved in AD. However, a key point that has been inadvertently underestimated or dismissed is the role of the protonated state at the C-terminal residue of amyloid-β peptides, which can give rise to intrinsic differences in the morphology and stability of the fibrils. For instance, the effects of the salt bridge formed between the C-terminal residue A42 and the residue K28 on the S-shaped Aβ protofibril structure remain unknown and may be different from those in the U-shaped Aβ protofibril structures. To address this effect, we explore the stability of the S-shaped protofibrils capped with different C-terminal modifications, including carboxyl group in its deprotonated (COO-) and protonated (COOH) states, by using molecular dynamics simulations. Our findings indicated that the C-terminal deprotonated protofibril is significantly more stable than its C-terminal protonated counterpart due to a well-defined and highly stable zipper-like salt-bridge-chain formed by the ϵ-NH3+ groups on the sidechain of residue K28 and the C-terminal COO- group at the A42 residue. The revealed underlying molecular mechanism for the different stability of the protofibrils provides insights into the diversity of polymorphism in Aβ fibrils.