[Central acetylcholinergic systems in the normal aged and in the patient with Alzheimer-type dementia (ATD)].
Since the function of the brain is considered to be a sum of synaptic transmission phenomena, information on both neurotransmitters and receptors are needed. In addition, experiments of behavioral pharmacology to determine whether the neuron network is in operation or not are indispensable. Acetylcholine (ACh) is difficult to measure in the postmortem brain because of rapid postmortem degradation, and thus the activity of choline acetyltransferase (CAT), a synthetic enzyme, is determined. Receptors for ACh system are classified into muscarinic ACh receptors (MCR) and nicotinic ACh receptors (NCR). Since ACh and MCR/NCR are contained in different neurons, their regional distributions mismatch. Therefore, to evaluate the relationship between the ACh neuronal system and aging or dementia, information on all steps of CAT, receptors, memory and learning experiments are needed. Both in the normally aged brain and ATD brain, the ACh neuronal system at all steps is decreased except an increase in ACh degradation enzyme (acetylcholinesterase) in the normally aged brain. In animals, the decreased ACh neural system associated with aging can be normalized by drugs, showing that the aged brain still has plasticity. On the other hand, autoradiography of MCR in the ATD brain demonstrated destruction of the laminar structure of the cerebral cortex. This suggests that drugs to increase only ACh are not effective for treating ATD. In ATD, treatment methods that prevents structural destruction or its progression should be developed.