Hippocampal level of neural specific adenylyl cyclase type I is decreased in Alzheimer's disease.
Previous studies reported disruption of adenylyl cyclase (AC)-cyclic AMP (cAMP) signal transduction in brain of Alzheimer's disease (AD). We also demonstrated that basal and stimulated AC activities in the presence of calcium and calmodulin (Ca(2+)/CaM) were significantly decreased in AD parietal cortex. In the present study, we examined the amounts of Ca(2+)/CaM-sensitive types I and VIII AC, and Ca(2+)/CaM-insensitive type VII AC in the postmortem hippocampi from AD patients and age-matched controls using immunoblotting. The specificities of the anti-type VII and VIII AC antibodies were confirmed by preabsorption with their specific blocking peptides. We observed a significant decrease in the level of type I AC and a tendency to decrease in the level of type VIII AC in AD hippocampus. On the other hand, the level of type VII AC showed no alteration between AD and controls. A body of evidence from the studies with invertebrates and vertebrates suggests that types I and VIII AC may play an essential role in learning and memory. Our finding thus firstly demonstrated that a specific disruption of the Ca(2+)/CaM-sensitive AC isoforms is likely involved in the pathophysiology in AD hippocampus.
Yamamoto
M
M
Department of Psychiatry and Psychotherapy, University of Würzburg, Germany. yamamoto@mail.uni-wuerzburg.de
Götz
M E
ME
Ozawa
H
H
Luckhaus
C
C
Saito
T
T
Rösler
M
M
Riederer
P
P
D000262:Adenylyl Cyclases / Q000032:analysis* / Q000276:immunology; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000906:Antibodies / Q000276:immunology; D002118:Calcium; D002147:Calmodulin; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology; D011180:Postmortem Changes; D013997:Time Factors
D000906:Antibodies; D002147:Calmodulin; D007527:Isoenzymes; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C118292:adenylyl cyclase 8; D002118:Calcium