Reduced immunoreactivity of adenylyl cyclase in dementia of the Alzheimer type

THE amounts of three adenylyl cyclase (AC) subtypes in membranes from brain obtained post-mortem from patients with dementia of Alzheimer type (DAT) and controls were studied by Western blotting using polyclonal antibodies. AC subtypes were characterized by preabsorption by complementary peptides, species difference, tissue distribution and by using AC-VI-transfected cells. Immunoreactivities of AC-I and AC-II subtypes, which are predominant in brain tissue were decreased 40.5% (p<0.02) and 52.0% (p<0.02), respectively in DAT compared with controls. No significant difference in immunoreactivity of AC-V/VI subtypes distributed in various other tissues was observed. Our results are the first to indicate that reduced levels of brain-specific AC subtypes occur in DAT.