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.
Bibliographical noteFunding 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.