DECREASED BETA-ADRENOCEPTOR-STIMULATED ADENYLYL-CYCLASE ACTIVITY IN LYMPHOCYTES FROM ALZHEIMERS-DISEASE PATIENTS

Previous studies have shown that in Alzheimer's disease post-mortem br ain there are disruptions of both beta 1-adrenoceptor-G-protein coupli ng and G-protein stimulation of adenylyl cyclase activity. Decreased b eta-adrenoceptor stimulated adenylyl cyclase activity has also been sh own in Alzheimer's disease primary skin fibroblasts. In the present st udy, we determined the regulation of adenylyl cyclase in Alzheimer's d isease patients using an easily accessible tissue source, namely perip heral blood lymphocytes. beta-Adrenoceptor- and forskolin-stimulated a denylyl cyclase activities were investigated in lymphocytes from 12 Al zheimer's disease and 12 carefully matched and selected control subjec ts. No significant differences were found in basal or forskolin-stimul ated enzyme activities between Alzheimer's disease and control lymphoc ytes. In contrast, isoprenaline-stimulated adenylyl cyclase activities were significantly lower in the Alzheimer's disease groups, as compar ed to controls. These results indicate that there is a widespread disr uption of beta-adrenoceptor-G-protein-enzyme coupling in different tis sues from Alzheimer's disease patients, and that adenylyl cyclase dist urbances previously reported in Alzheimer's disease brain do not occur as a consequence of disease pathology or of terminal illness. (C) 199 7 Elsevier Science Ireland Ltd.