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

Research output: Contribution to journalArticlepeer-review

349 Scopus citations


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 languageEnglish (US)
Pages (from-to)157-161
Number of pages5
JournalNature neuroscience
Issue number2
StatePublished - Feb 1999

Bibliographical 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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