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.