FEATURE ARTICLE
Alzheimer's Disease
The molecular origins of the disease are coming to light, suggesting several novel therapies
Vernon Ingram
Available Treatments
Thirty years ago, studies of degeneration patterns in Alzheimer's disease identified substantial decreases among groups of neurons in the basal forebrain. These cells all used the transmitter acetylcholine, and their loss meant that less acetylcholine was being released at their former terminals in the cortex. The finding was important because cholinergic neurons in the cortex are involved in regulating attention, the first stage of learning and memory.
This knowledge led to the first (and only) Federal Drug Administration–approved drugs for Alzheimer's disease treatment, marketed under the trade names Aricept, Cognex and Exelon. All three work by prolonging the effects of individual acetylcholine-release events. They do this by inhibiting the enzyme acetylcholinesterase, which normally breaks down the neurotransmitter in the space between cells. This breakdown process goes on unabated even when there is too little acetylcholine being released, as is the case in Alzheimer's disease. By preventing acetylcholine metabolism, the levels of free neurotransmitter can be artificially raised. Unfortunately, clinical trials show that the improvement in memory is small and transient, whereas the side effects can be troublesome. In Europe the compound memantine, an inhibitor of a different (nonAMPA) glutamate-sensitive channel, is used for "age-related dementia" with some reported benefits.
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