Potent anti-angiogenic motifs within the Alzheimer beta-amyloid peptide

A beta peptides are the major constituents of senile plaques and cerebrovascular deposits in the brains of patients with Alzheimer's disease. We have shown previously that A beta(1-40) and A beta(1-42) peptides are potently anti-angiogenic both in vitro and in vivo. The current study characterizes important sequences within the A beta peptide that are required to exert its anti-angiogenic activity. We have used human umbilical vein endothelial cells to assess the anti-angiogenic activity of short fragments of A beta in vitro in a Matrigel network assay and in vivo in a rat corneal model of angiogenesis. The anti-angiogenic activity of these short peptide fragments is not related to effects on apoptosis or necrosis. Using normal and mutated peptide fragments, we show that the sequence VHHQKLVFF is sufficient to exhibit potent anti-angiogenic effects. This small peptide may therefore have clinical relevance as an anti-angiogenic agent.