Decrease in Adenylate Cyclase Activity Antecedes Neurofibrillary Tangle Formation

In previous studies, the formation of cAMP was seen to be significantly reduced in various brain regions in Alzheimer patients. Recently, a staging system was introduced in which Alzheimer-related histopathological changes were classified according to the pattern of alterations rather than their density. In this study, we examined the degree of correlation between these stages and the postmortem activity of the cAMP-generating enzyme adenylate cyclase. Our findings suggest that forskolin-stimulated adenylate cyclase activity is significantly decreased before major neurofibrillary changes develop. Early impairment of postreceptor signalling could have potentially important consequences for drug treatment and/or for the development of neurofibrillary changes.