SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein

Costantino Iadecola; Fangyi Zhang; Kiyoshi Niwa; Chris Eckman; Sherry K. Turner; Elizabeth Fischer; Steven Younkin; David R. Borchelt; Karen K. Hsiao; George A. Carlson

doi:10.1038/5715

SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein

Costantino Iadecola, Fangyi Zhang, Kiyoshi Niwa, Chris Eckman, Sherry K. Turner, Elizabeth Fischer, Steven Younkin, David R. Borchelt, Karen K. Hsiao, George A. Carlson

Neuroscience

Research output: Contribution to journal › Article › peer-review

329 Scopus citations

Abstract

Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium- dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia.

Original language	English (US)
Pages (from-to)	157-161
Number of pages	5
Journal	Nature Neuroscience
Volume	2
Issue number	2
DOIs	https://doi.org/10.1038/5715
State	Published - Feb 1999

ASJC Scopus subject areas

General Neuroscience

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title = "SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein",

abstract = "Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium- dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia.",

author = "Costantino Iadecola and Fangyi Zhang and Kiyoshi Niwa and Chris Eckman and Turner, {Sherry K.} and Elizabeth Fischer and Steven Younkin and Borchelt, {David R.} and Hsiao, {Karen K.} and Carlson, {George A.}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health (NS34179, NS37853, NS35806 to C.I.; NS33249 to K.K.H; AG10681 to G.A.C.) and the Fraternal Order of Eagles (G.A.C.). We thank G. Perry for the oxidative stress data and Karen MacEwan for editorial assistance.",

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AU - Iadecola, Costantino

AU - Zhang, Fangyi

AU - Niwa, Kiyoshi

AU - Eckman, Chris

AU - Turner, Sherry K.

AU - Fischer, Elizabeth

AU - Younkin, Steven

AU - Borchelt, David R.

AU - Hsiao, Karen K.

AU - Carlson, George A.

N1 - Funding Information: This work was supported by grants from the National Institutes of Health (NS34179, NS37853, NS35806 to C.I.; NS33249 to K.K.H; AG10681 to G.A.C.) and the Fraternal Order of Eagles (G.A.C.). We thank G. Perry for the oxidative stress data and Karen MacEwan for editorial assistance.

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N2 - Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium- dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia.

AB - Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium- dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia.

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SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein

Abstract

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