beta-Amyloid (12-28)

Abeta(12-28) residues are the binding site for apolipoprotein E (apoE) on Abeta. This sequence encompasses a hydrophobic domain (residues 14-21) and a beta-turn (residues 22–28) which place two hydrophobic domains of Abeta 14 to 21 and 29 to 40/42 opposite each other, allowing for the assembly of Abeta peptides into fibrils. The secondary structure of Aß (12- 28), a neutral peptide, is dominated by beta-helix and random coil. The interaction of apoE with residues 12 to 28 of Aß is not just a non-specific hydrophobic interaction but plays a pivotal role in the mechanism of Abeta pathology in Alzheimer’s disease (AD). Beta-amyloid (12-28) and five other fragments enhanced aggregation of full length Abeta (1-40). All of the peptides that enhance aggregation contained either residues 17 to 20 or 30 to 35, indicating the importance of these regions for promoting aggregation of full-length Abeta.