Reduced cAMP-signal transduction in postmortem hippocampus of demented old people

The basal as well as the stimulated activity of the adenylate cyclase was determined in postmortem hippocampi. The tissue probes were obtained from 12 demented individuals (10 Alzheimer-type dementia; 1 Down's syndrome; 1 argyrophilic grains syndrome) and from 15 age-matched controls. The diagnoses were done in accordance with histopathological criteria. Adenylate cyclase was stimulated by isoprenaline, Gpp(NH)p, or forskolin. The amount of cAMP formed was determined by the protein binding method using a radioimmuno assay. In tissues of controls as well as of demented patients adenylate cyclase was stimulated in the rank order of isoprenaline less than Gpp (NH) p less than forskolin. In hippocampal tissues of demented individuals a significant reduction (50%, p less than 0.01) in basal as well as stimulated adenylate cyclase activity was found. This reduction in cAMP signal transduction is not caused by simple cell loss.