Each perturbation observed in AD has been considered for potential therapeutic manipulation. AD involves a combina-
tion of deranged amyloid processing and metabolism, neurotoxicity, inflammatory response, loss of synaptic connections (especially cholinergic), and secondary cell senescence and death. Accumulation of amyloid and defects in amyloid processing has proven difficult as a target for therapy. The inflammatory reaction seen in the brain and oxidative stress have led to the long-term use of nonsteroidal anti-inflammatory drugs, which have been shown in some studies to decrease the risk of AD (10). Alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) may slow the progress of the disease
(11). The loss of cholinergic activity correlates well with the magnitude of the disease, but medical therapy with acetylcho-line, acetylcholine precursors, or cholinergic agonists has proven impractical due to the widespread nature of the cholin-ergic system throughout the body and the relative impermeability of the blood-brain barrier. Cholinesterase inhibitors, which work by preventing the breakdown of acetylcholine in the synapse, have achieved moderate success in clinical trials
(12). Most oral pharmacological therapy for AD uses this strategy. Examples of such medications in clinical use include tacrine, donepezil, rivastigmine, and galantamine (13). On the whole, all cholinergic medications have had only limited success.
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