Impairment of G_sα function in human brain cortex of Alzheimer’s disease: comparison with normal aging

Summary.

We examined the quantity and quality of G proteins in membrane preparations of post-mortem human brain, i.e. in parietal, temporal and occipital cortical regions, from normal subjects over age (17–89 years old) and with Alzheimer’s disease (AD) in comparison with aged-matched controls. In normal aging, the immunoreactivities determined of G_iα, G_qα and G_β were inversely correlated with age. The function of G proteins was examined by photoaffinity GTP analogue [azidoanilido GTP (AAGTP)] labelling. AAGTP labelling to G_sα and G_i/oα, and the ratio of G_sα to G_i/oα AAGTP labelling showed no age-dependent changes. In AD compared to age-matched controls, there were no significant differences in the levels of G_sHα, G_sLα, G_iα, G_oα, G_qα and G_β subunits. Functional effects of G proteins, however, as measured by AAGTP labelling to G_sα, but not to G_i/oα, was significantly decreased in AD compared to controls in the parietal and temporal cortex, but not in the occipital cortex. These results suggest that the disturbances of post-receptor trans-membrane signalling in AD can be attributed to functional changes of G_sα, and these are independent of alterations in the level for those proteins in normal aging.