Ca2+/CaM-sensitive adenylyl cyclase activity is decreased in the Alzheimer's brain: possible relation to type I adenylyl cyclase.

Immunoreactivities of four subtypes of adenylyl cyclase (AC) (types I, II, IV and V/VI), and basal, forskolin- and Mn(2+)-stimulated AC activities with or without calcium and calmodulin (Ca2+/CaM) were estimated in parietal cortex membranes from cases with dementia of the Alzheimer type (DAT) and age-matched controls. Immunoreactivities of AC-I and AC-II were significantly decreased, but those of AC-IV and AC-V/VI did not change in DAT brains. There was a significant correlation of AC-I immunoreactivity with Ca2+/CaM-sensitive AC activity, but not with the Ca2+/CaM-insensitive activity. Ca2+/CaM-sensitive AC activity was significantly lower in DAT than in the control, indicating that impairment of Ca2+/CaM-sensitive AC-I is clearly involved in the pathophysiology of DAT.