The purpose of this study was to compare the effects of aging and Alzheimer disease (AD) on the important intracellular signaling enzyme cAMP-dependent protein kinase A (PKA) in cerebral microvessels. PKA activity and levels were measured in microvessels isolated from the brains of adult and aged rodents as well as from the cerebral cortices of AD and elderly control patients. The results showed that cerebral microvessels from aged rats have significantly (p < 0.01) higher PKA activity and levels when compared to cerebral microvessels from adult rats. In contrast, no significant difference was found between PKA activity or levels in cerebral microvessels from AD patients when compared to controls. These results indicate that in cerebral microvessels both PKA activity and levels increase with age but are unaffected by AD. The data suggest that protein phosphorylation in brain microvessels may be affected differentially by aging and dementia.