Vitamin E but not 17beta-estradiol protects against vascular toxicity induced by beta-amyloid wild type and the Dutch amyloid variant.

[hereditary cerebral hemorrhage with amyloidosis]

Amyloid beta -peptide (Abeta ) 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 Abeta yielding Abeta (Glu 22 -->Gln ). The present study addresses the effect of amyloid fibrils from both wild-type and mutated Abeta on vascular cells , as well as the putative protective role of antioxidants on amyloid angiopathy . For this purpose , we studied the cytotoxicity induced by Abeta (1 -40 Glu 22 -->Gln ) and Abeta (1 -40 wild-type ) fibrils on human venule endothelial cells and rat aorta smooth muscle cells . We observed that Abeta (Glu 22 -->Gln ) fibrils are more toxic for vascular cells than the wild-type fibrils . We also evaluated the cytotoxicity of Abeta fibrils bound with acetylcholinesterase (AChE ), a common component of amyloid deposits . Abeta (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 Abeta fibrils on neuronal cells prompted us to test the effect of vitamin E , vitamin C , and 17 beta -estradiol on vascular damage induced by Abeta (wild-type ) and Abeta (Glu 22 -->Gln ). Our data indicate that vitamin E attenuated significantly the Abeta-mediated cytotoxicity on vascular cells , although 17 beta -estradiol and vitamin C failed to inhibit the cytotoxicity induced by Abeta fibrils .