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

Abstract
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.
AuthorsM Yamamoto, M E Götz, H Ozawa, C Luckhaus, T Saito, M Rösler, P Riederer
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1535 Issue 1 Pg. 60-8 (Dec 15 2000) ISSN: 0006-3002 [Print] Netherlands
PMID11113632 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies
  • Calmodulin
  • Isoenzymes
  • Cyclic AMP
  • Adenylyl Cyclases
  • adenylyl cyclase 1
  • adenylyl cyclase 8
  • Calcium
Topics
  • Adenylyl Cyclases (analysis, immunology)
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease (enzymology, pathology)
  • Antibodies (immunology)
  • Calcium
  • Calmodulin
  • Cyclic AMP (metabolism)
  • Down-Regulation
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Hippocampus (enzymology, pathology)
  • Humans
  • Immunoblotting
  • Isoenzymes (analysis)
  • Male
  • Middle Aged
  • Neurons (enzymology)
  • Postmortem Changes
  • Time Factors

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