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.
Clinical Neurochemistry and NPF Center of Excellence Research Labs., Department of Psychiatry, University of Würzburg, Germany.
E
E
Hashimoto
H
H
Ozawa
T
T
Saito
W
W
Gsell
N
N
Takahata
P
P
Riederer
L
L
Frölich
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