We have developed a model for the onset of Alzheimers disease that involves the interaction between acetylcholine and beta-amyloid. The model is based on the experimental finding that binding of beta-amyloid to p75 receptors of cholinergic neurons leads to apoptosis. The loss of the cholinergic neurons, in turn, causes a decrease in the concentration of acetylcholine. Thus, increased beta-amyloid causes a loss of acetylcholine. It has previously been shown that a decrease in the concentration of acetylcholine causes an increase in the concentration of beta-amyloid. Thus, there is positive feedback between increased beta-amyloid and decreased acetylcholine. We have developed a mathematical model to describe this positive feedback. The model shows an initial slow decrease in acetylcholine and a subsequent much faster decrease. Current therapy for Alzheimers disease involves the use of acetylcholinesterase inhibitors to attempt to overcome the loss of acetylcholine. According to our model, the efficacy of this approach would be very much enhanced if treatment is started relatively early, before the positive feedback has much impact. - Alzheimer's disease, beta-amyloid, apoptosis, acetylcholine, choline
