This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer disease (AD) is a chronic disorder that progressively leads to the loss of cognitive functions, with synaptic loss appearing as a critical element in the development of the disease. Neurochemical studies have suggested that the cholinergic neurons in the neocortex and hippocampus are those predominantly affected in AD (Bartus et al., 1982;Dunnet et al., 1993;Weinstock, 1997), a fact that likely accounts for the strong decrease in neurotransmitter acetylcholine (ACh) levels in AD victims'brains. Symptomatic treatment has therefore, so far, focused upon restoring cholinergic neurotransmission. Acetylcholinesterase (AChE) is the enzyme responsible for ACh hydrolysis, hence it is the target of most currently used anti-Alzheimer drugs.