Hippocampal level of neural specific adenylyl cyclase type I is decreased in Alzheimer’s disease

AbstractPrevious 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 (Ca2+/CaM) were significantly decreased in AD parietal cortex. In the present study, we examined the amounts of Ca2+/CaM-sensitive types I and VIII AC, and Ca2+/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 Ca2+/CaM-sensitive AC isoforms is likely involved in the pathophysiology in AD hippocampus