This study investigates the arrest of β-amyloid (Aβ) fibril formation using a pentapeptide ligand, KLVFF (Aβ16-28). The researchers found that peptides incorporating this short Aβ fragment can bind to full-length Aβ and prevent its assembly into amyloid fibrils. Through alanine substitution, they identified that amino acids Lys16, Leu17, and Phe28 are crucial for binding and inhibiting Aβ fibril formation. A mutant Aβ molecule with these residues substituted showed a significantly reduced ability to form amyloid fibrils. The findings suggest that residues Aβ16-28 serve as a binding sequence during Aβ polymerization and fibril formation. The KLVFF peptide may serve as a lead compound for developing peptide and non-peptide agents to inhibit Aβ amyloidogenesis in vivo. The study also highlights the importance of the C-terminal region of Aβ in Aβ polymerization and the potential of small peptide ligands in treating Alzheimer's disease.This study investigates the arrest of β-amyloid (Aβ) fibril formation using a pentapeptide ligand, KLVFF (Aβ16-28). The researchers found that peptides incorporating this short Aβ fragment can bind to full-length Aβ and prevent its assembly into amyloid fibrils. Through alanine substitution, they identified that amino acids Lys16, Leu17, and Phe28 are crucial for binding and inhibiting Aβ fibril formation. A mutant Aβ molecule with these residues substituted showed a significantly reduced ability to form amyloid fibrils. The findings suggest that residues Aβ16-28 serve as a binding sequence during Aβ polymerization and fibril formation. The KLVFF peptide may serve as a lead compound for developing peptide and non-peptide agents to inhibit Aβ amyloidogenesis in vivo. The study also highlights the importance of the C-terminal region of Aβ in Aβ polymerization and the potential of small peptide ligands in treating Alzheimer's disease.