Abstract

Amyloid ?-peptide (A?) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in A? yielding A?Glu22?Gln. The present study addresses the effect of amyloid fibrils from both wild-type and mutated A? on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by A?1-40 Glu22?Gln and A?1-40 wild-type fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that A?Glu22?Gln fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of A? fibrils bound with acetyl-cholinesterase (AChE), a common component of amyloid deposits. A?1-40 wild-type-AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of A? fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17?-estradiol on vascular damage induced by A?wild-type and A?Glu22?Gln. Our data indicate that vitamin E attenuated significantly the A?-mediated cytotoxicity on vascular cells, although 17?-estradiol and vitamin C failed to inhibit the cytotoxicity induced by A? fibrils.