SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein.
Peptides derived from proteolytic processing of the beta-amyloid precursor protein (APP), including the amyloid-beta 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.
Iadecola
C
C
Department of Neurology, University of Minnesota, Minneapolis 55455, USA. iadec001@tc.umn.edu
Zhang
F
F
Niwa
K
K
Eckman
C
C
Turner
S K
SK
Fischer
E
E
Younkin
S
S
Borchelt
D R
DR
Hsiao
K K
KK
Carlson
G A
GA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D016166:Free Radical Scavengers; C000606290:SOD1 protein, human; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1