Physiological levels of amyloid peptides stimulate the angiogenic response through FGF-2.

Amyloid beta peptides (Abeta) form insoluble aggregates in Alzheimer's disease. Accumulation of misfolded amyloid fibrils is generally believed to be a key pathogenic event in several brain disorders. Here we show that small amounts of Abeta peptides activate angiogenesis by promoting endothelial cell proliferation and migration as well as pseudocapillary formation. Abeta peptides functionally synergize with fibroblast growth factor (FGF-2) to promote c-Raf and ERK1/2 activation and angiogenesis in vivo. Thus, Abeta peptides at nanomolar concentrations prime FGF-2 effects on the endothelium, enhancing survival and sustaining angiogenesis. The angiogenesis promoted by Abeta peptides via FGF-2 might have implications for understanding the initial stages of Alzheimer's disease and for the design of therapies targeting beta amyloid.