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

Aβ 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 Aβ1–40 and Aβ1–42 peptides are potently anti-angiogenic both in vitro and in vivo. The current study characterizes important sequences within the Aβ 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 Aβin 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.