Acetylcholine in AD: Expectations meet reality

Summary

The neuropharmacological consequences of finding evidence for deficient acetylcholine neurotransmission in AD have been complex. The initial optimism for a quick cure from choline or lecithin precursor administration, inspired by the success of levodopa in Parkinson’s disease, quickly faded when put to the test. Nonetheless, the cholinergic hypothesis of memory dysfunction in AD was valid, and eventually it led to the introduction of AChEI drugs to increase acetylcholine transmission. Drugs of this class are the mainstays of current treatment for AD, even though their effects are generally modest. In the search for improved symptomatic and possibly neuroprotective treatments, acetylcholine may have an unexpected role. The observation that M1 and M3 receptor stimulation with cholinergic drugs drives APP processing into the α-secretase pathway adds a modern coda to the acetylcholine-AD story that is still unfinished.