Increasing evidence suggests that up-regulation of the cAMP-second messenger system is implicated in Alzheimer's disease neurodegeneration. Since previous studies reported an increased level of cAMP in microvessels of Alzheimer's patients compared with those from non-demented elderly controls, we have carried out an immunohistochemical study to compare cAMP immunostaining in brain vessels from patients with dementia and neuropathological criteria of Alzheimer's disease (n=5) with those of age-matched patients (n=10). We have also included a control group of adult patients (n=5) to evaluate the role of aging separate from the effects of dementia. Our results demonstrated an increased cAMP immunostaining in cerebral cortical and meningeal vessels from Alzheimer's patients compared to nondemented elderly and adult controls. Vascular cAMP immunostaining was mainly observed in frontal and temporal cortex, the hippocampus being the region that showed the more intense and widespread vascular cAMP immunostaining. We also observed a conspicuous vascular beta-amyloid immunostaining specifically in those vessels that showed the highest cAMP immunostaining. We suggest that increased vascular cAMP immunostaining is mainly localised in the selectively vulnerable targets of neurodegeneration that characterise AD. Moreover, the co-immunolocalisation of cAMP and beta-amyloid protein in cerebral vessels of patients with AD suggests a possible role of cAMP up-regulation in the accumulation of those amyloidogenic peptides.