Impairment of G(salpha) function in human brain cortex of Alzheimer's disease: comparison with normal aging.
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(ialpha), G(qalpha) and G(beta) were inversely correlated with age. The function of G proteins was examined by photoaffinity GTP analogue [azidoanilido GTP (AAGTP)] labelling. AAGTP labelling to G(salpha) and G(i/oalpha), and the ratio of G(salpha) to G(i/oalpha) AAGTP labelling showed no age-dependent changes. In AD compared to age-matched controls, there were no significant differences in the levels of G(sHalpha), G(sLalpha), G(ialpha), G(oalpha), G(qalpha) and G(beta) subunits. Functional effects of G proteins, however, as measured by AAGTP labelling to G(salpha), but not to G(i/oalpha), 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(salpha), and these are independent of alterations in the level for those proteins in normal aging.
Hashimoto
E
E
Clinical Neurochemistry and NPF Center of Excellence Research Labs., Department of Psychiatry, University of Würzburg, Germany.
Ozawa
H
H
Saito
T
T
Gsell
W
W
Takahata
N
N
Riederer
P
P
Frölich
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D001386:Azides; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives*; D006801:Humans; D015151:Immunoblotting; D008875:Middle Aged; D019920:Photoaffinity Labels; D011180:Postmortem Changes; D013570:Synaptic Membranes / Q000378:metabolism; D013997:Time Factors
D001386:Azides; D019920:Photoaffinity Labels; C031907:GTP gamma-4-azidoanilide; D006160:Guanosine Triphosphate; D019205:GTP-Binding Protein alpha Subunits, Gs