Convergent cholinergic activities in aging and Alzheimer's disease

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities have been examined postmortem in a series of 66 individuals with no evidence of CNS disease, ranging in age from 24 gestational weeks to 95 years and in 33 cases of Alzheimer's disease (AD) aged 57-89 years. In the normal human hippocampus a striking and highly significant age-related decline in ChAT occurred from middle to old age (between 40 and 100 years); a trend apparent at a later stage and to a lesser extent in the hippocampal gyrus. In both areas enzyme activity in AD was inversely related to age at death; reductions compared with the normal were on average 70-80% in the 60-70 year old groups compared with 30-40% in the 80-90 year old group. A similar trend was apparent with respect to acetylcholinesterase (AchE) histochemical activity associated with fibers and terminals (predominantly cholinergic and concentrated in CA3 and 4 of the hippocampus) but not with reactive perikarya (considered to be noncholinergic) present in both hippocampus and cortex. These data indicate that the normal aging human hippocampus may constitute a useful model for investigating the dysfunction or degeneration of basal forebrain cholinergic neurons in AD.