Receptor-mediated activation of G proteins is reduced in postmortem brains from Alzheimer's disease patients.

The effects of Alzheimer's disease (AD) on [35S]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 [35S]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 [35S]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 [35S]GTP gamma S binding to G proteins may be a result of decoupling between receptors and their associated G proteins.