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 pa thogenesis of Alzheimer's dementia. We found that transgenic mice overexpre ssing APP have a profound and selective impairment in endothelium-dependent regulation of the neocortical microcirculation. Such endothelial dysfuncti on was not found in transgenic mice expressing both APP and superoxide dism utase-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 an d to neuronal dysfunction in Alzheimer's dementia.