IMPAIRED G-PROTEIN-STIMULATED ADENYLYL-CYCLASE ACTIVITY IN ALZHEIMERS-DISEASE BRAIN IS NOT ACCOMPANIED BY REDUCED CYCLIC-AMP-DEPENDENT PROTEIN-KINASE-A ACTIVITY

Previous studies have shown that the regulation of adenylyl cyclase ac tivity is disrupted in Alzheimer's disease postmortem brain. In the pr esent study, we determined whether disrupted adenylyl cyclase is accom panied by altered cAMP-dependent protein kinase activity in Alzheimer' s disease superior temporal cortex and cerebellum. GTP gamma S-stimula ted adenylyl cyclase activity was significantly lower in Alzheimer's d isease superior temporal cortex, but not cerebellum, compared to value s from a series of matched control cases. Neither basal or forskolin-s timulated adenylyl cyclase activities were significantly different bet ween the Alzheimer's disease and control brain regions. No significant differences were seen in either particulate or soluble fraction cAMP- dependent protein kinase activities between the Alzheimer's disease an d control brain regions. It is concluded that disrupted adenylyl cycla se signalling in Alzheimer's disease brain occurs specifically at the level of G(s)-protein-enzyme interactions and is not accompanied by an altered cAMP-dependent protein kinase activity.