[Function and amount of GTP binding proteins in postmortem human brain in dementia of the Alzheimer's type]

Qualitative or quantitative alterations of GTP binding (G) proteins in membrane preparations from parietal cortex and temporal cortex in postmortem human brain obtained from patients with dementia of the Alzheimer's type (DAT) and aged and postmortem delay matched controls were investigated by immunoblotting with polyclonal antibodies (RM/1, AS/7, GC/2, QL, SW/1) against specific G protein (Gs alpha, Gi alpha, Go alpha, Gq alpha, G beta, respectively) and the functional photoaffinity GTP analog [azidoanilido GTP (AAGTP)] labeling. Although the quantitative immunoreactivity showed no significant differences between the two groups, a marked reduction in AAGTP binding to Gs alpha was seen in the DAT group compared with controls in both parietal and temporal cortex. Moreover, the ratio of Gs alpha to Gi/o alpha AAGTP binding decreased significantly in the same regions of the DAT group. These results suggest that the disturbances of G protein mediated signal transduction may be involved in the pathophysiology of DAT.