Here is another Alzheimer neuritic plaque seen with a silver stain that highlights the dystrophic neurites. The major biochemical defect in Alzheimer disease (AD) is a loss of acetylcholine in the cerebral cortex. Cholinesterase inhibitors, which increase the availability of acetylcholine in central synapses, include the drugs tacrine, donepezil, metrifonate, rivastigmine and galantamine, have been employed in the treatment of AD. In addition to an effect on improved cognition and slowing of cognitive decline, they have a positive effect on mood and behavior. The length of the effect is uncertain. The majority of patients with Alzheimer disease have at least one copy of apolipoprotein E4, and these patients seem to have a greater impairment of presynaptic cholinergic function than patients without the apolipoprotein E4 allele, and this might be expected to reduce their response to treatment.