ARREST OF BETA-AMYLOID FIBRIL FORMATION BY A PENTAPEPTIDE LIGAND

Polymerization of amyloid beta-peptide (A beta) into amyloid fibrils i s a critical step in the pathogenesis of Alzheimer's disease, Here, we show that peptides incorporating a short A beta fragment (KLVFF; A be ta(16-20)) can bind full-length A beta and prevent its assembly into a myloid fibrils, Through alanine substitution, it was demonstrated that amino acids Lys(16), Leu(17) and Phe(20) are critical for binding to A beta and inhibition of A beta fibril formation, A mutant A beta mole cule, in which these residues had been substituted, had a markedly red uced capability of forming amyloid fibrils. The present data suggest t hat residues A beta(16-20) serve as a binding sequence during A beta p olymerization and fibril formation, Moreover, the present KLVFF peptid e may serve as a lead compound for the development of peptide and nonp eptide agents aimed at inhibiting A beta amyloidogenesis in vivo.