Objectives. To present available research evidence suggesting a possibility of cholinergic modulation of β-APP metabolism and its theoretical implications for Alzheimer's disease treatment.
Views. Leading hypotheses concerning Alzheimer's disease (AD) consider dysfunction of β-APP metabolism as the basic pathogenic mechanism (the amyloid cascade hypothesis), and a cholinergic neurotransmission disorder as a neurochemical background for clinically observed cognitive and behavioral pathology (the cholinergic hypothesis). Molecular and clinical studies support the idea that β-APP metabolism products interact with the cholinergic system in a quite complicated manner. Beta-amyloid may be particularly toxic to cholinergic neurons, and may lead to a deficiency of acetylcholine biosynthesis. On the other hand, cholinergic dysfunction may lead to an overproduction and cerebral deposition of amyloid β.
Conclusions. Cholinesterase inhibitors facilitating neurotransmission within the cholinergic synapse may produce a more than symptomatic effect, possibly via modulation of β-APP metabolism. Although data obtained in recent years support the view about a possible effect of cholinesterase inhibitors on the natural course of AD, they are not conclusive yet.