RT Journal Article
SR Electronic
T1 Vitamin E But Not 17β-Estradiol Protects against Vascular Toxicity Induced by β-Amyloid Wild Type and the Dutch Amyloid Variant
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3081
OP 3089
DO 10.1523/JNEUROSCI.22-08-03081.2002
VO 22
IS 8
A1 Francisco J. Muñoz
A1 Carlos Opazo
A1 Gabriel Gil-Gómez
A1 Gladys Tapia
A1 Virginia Fernández
A1 Miguel A. Valverde
A1 Nibaldo C. Inestrosa
YR 2002
UL http://www.jneurosci.org/content/22/8/3081.abstract
AB Amyloid β-peptide (Aβ) 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 Aβ yielding AβGlu22→Gln. The present study addresses the effect of amyloid fibrils from both wild-type and mutated Aβ on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by Aβ1–40 Glu22→Gln and Aβ1–40 wild-type fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that AβGlu22→Gln fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of Aβ fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. Aβ1–40 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 Aβ fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17β-estradiol on vascular damage induced by Aβwild-type and AβGlu22→Gln. Our data indicate that vitamin E attenuated significantly the Aβ-mediated cytotoxicity on vascular cells, although 17β-estradiol and vitamin C failed to inhibit the cytotoxicity induced by Aβ fibrils.