DISRUPTED BETA-1-ADRENOCEPTOR G-PROTEIN COUPLING IN THE TEMPORAL CORTEX OF PATIENTS WITH ALZHEIMERS-DISEASE

The efficacy of beta1-adrenoceptor-G protein coupling was studied in postmortem temporal cortex synaptic membranes from a series of control and Alzheimer's disease subjects. For the control cases, the non-hydrolysable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) gave a significant reduction in the affinity of the agonist isoprenaline to displace binding of the radiolabelled antagonist (+/-)-4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-H-3]benzimidazol-2-one ([H-3]CGP- 12177). This effect was attributed to the conversion of high agonist-affinity sites to a lower-affinity state and was not found for the Alzheimer's disease cases. These data indicate that a disruption of beta1-adrenoceptor-G protein coupling occurs in the temporal cortex of Alzheimer's disease patients.