RECEPTOR-MEDIATED ACTIVATION OF G-PROTEINS IS REDUCED IN POSTMORTEM BRAINS FROM ALZHEIMERS-DISEASE PATIENTS

The effects of Alzheimer's disease (AD) on [S-35]GTP gamma S binding to G proteins was examined in postmortem cerebrocortex. Stimulation of the beta-adrenergic or muscarinic cholinergic receptors in control tissue with selective agonists resulted in increases in [S-35]GTP gamma S binding to G alpha proteins in a receptor-specific fashion. The responses were markedly reduced in brain tissues from AD patients. In contrast, basal [S-35]GTP gamma S binding to the G alpha proteins was relatively intact in AD brains. Immunoblot analyses reveal that levels of cerebrocortical G alpha proteins in AD are not altered. The results suggest that in AD the decrease in agonist-stimulated [S-35]GTP gamma S binding to G proteins may be a result of decoupling between receptors and their associated G proteins.