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 (c AMP) signal transduction in brain of Alzheimer's disease (AD). We also demo nstrated that basal and stimulated AC activities in the presence of calcium and calmodulin (Ca2+/CaM) were significantly decreased in AD parietal cort ex. In the present study, we examined the amounts of Ca2+/CaM-sensitive typ es I and VIII AC, and Ca2+/CaM-insensitive type VII AC in the postmortem hi ppocampi from AD patients and age-matched controls using immunoblotting. Th e specificities of the anti-type VII and VIII AC antibodies were confirmed by preabsorption with their specific blocking peptides. We observed a signi ficant 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 t ype 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-sensit ive AC isoforms is likely involved in the pathophysiology in AD hippocampus . (C) 2000 Elsevier Science B.V. All rights reserved.