The mechanisms of interfacial folding and membrane insertion of the Alzheimer's amyloid-beta fragment Abeta(25-35) and its less toxic mutant, N27A-Abeta(25-35) and more toxic mutant, M35A-Abeta(25-35), are investigated using replica-exchange molecular dynamics in an implicit water-membrane environment. This study simulates the processes of interfacial folding and membrane insertion in a spontaneous fashion to identify their general mechanisms. Abeta(25-35) and N27A-Abeta(25-35) peptides share similar mechanisms: the peptides are first located in the membrane hydrophilic region where their C-terminal residues form helical structures. The peptides attempt to insert themselves into the membrane hydrophobic region using the C-terminal or central hydrophobic residues. A small portion of peptides can successfully enter the membrane's hydrophobic core, led by their C-terminal residues, through the formation of continuous helical structures. No detectable amount of M35A-Abeta(25-35) peptides appeared to enter the membrane's hydrophobic core. The three studied peptides share a similar helical structure for their C-terminal five residues, and these residues mainly buried within the membrane's hydrophobic region. In contrast, their N-terminal properties are markedly different. With respect to the Abeta(25-35), the N27A-Abeta(25-35) forms a more structured helix and is buried deeper within the membrane, which may result in a lower degree of aggregation and a lower neurotoxicity; in contrast, the less structured and more water-exposed M35A-Abeta(25-35) is prone to aggregation and has a higher neurotoxicity. Understanding the mechanisms of Abeta peptide interfacial folding and membrane insertion will provide new insights into the mechanisms of neurodegradation and may give structure-based clues for rational drug design preventing amyloid associated diseases.