Area specific alterations in muscarinic stimulated low Km GTPase activity in aging and Alzheimer's disease: implications for altered signal transduction.

Carbachol-stimulated low Km GTPase activity (an index of muscarinic receptor-G protein coupling) was examined in hippocampus, basal ganglia, orbital frontal gyrus and superior frontal gyrus obtained from mature, aged and Alzheimer's Disease (AD) groups. Results indicated that carbachol-stimulated low Km GTPase activities in basal ganglia were as follows: mature controls > aged > AD, and there was a trend toward a similar pattern of decline in the hippocampus. No differences were seen in the two cortical areas examined; however, carbachol-stimulated low Km GTPase activity was small in the mature controls. Importantly, there were significant negative correlations between disease duration and carbachol-stimulated low Km GTPase activity in all areas examined except the orbital frontal gyrus. The longer the duration of the disease the lower the carbachol-stimulated low Km GTPase activity. Results suggest that age and disease-related changes in mAChR-G protein interactions in the basal ganglia may contribute to reduced signal transduction (ST). In addition, since decreased carbachol-stimulated low Km GTPase activity has also been observed in the aged rat; thus, investigations of the factors involved in decrements in signal transduction in the aged rat may be useful for understanding these alterations in aged humans or victims of AD.