Supplementation of Nitric Oxide Attenuates AβPP and BACE1 Protein in Cerebral Microcirculation of eNOS-Deficient Mice

Recently, we demonstrated in endothelial nitric oxide synthase deficient (eNOS(-/-)) mice that loss of endothelial NO led to increased protein levels of amyloid-beta protein precursor (A beta PP), beta-site A beta PP cleaving enzyme 1 (BACE1), and amyloid-beta (A beta) peptide. Therefore, our aim was to determine if NO supplementation in vivo would attenuate A beta PP and BACE1 protein levels. cGMP levels were significantly increased while A beta PP and BACE1 protein levels were statistically lower in cerebral microvessels from nitroglycerin-treated eNOS(-/-) mice as compared to vehicle-treated mice. Our findings support the concept that preservation of NO/cGMP signaling is an important modulator of expression and processing of A beta PP.