Cholinergic hypothesis of Alzheimer’s disease

Professor Donna Wilcock dscusses the cholinergic hypothesis of Alzheimer's disease, which focuses on cholinergic neurons. The hypothesis has not been supported.

The cholinergic hypothesis of Alzheimer’s disease stems from some early studies that showed, early in the Alzheimer’s disease process, the cholinergic neurons that project from the lower brain areas up to the higher brain areas that are involved in memory, that these are selectively lost early in Alzheimer’s disease. This finding guided us to look for ways to increase acetylcholine or protect these neurons in some way, and obviously that led to the development of Aricept. Aricept is what we call an acetylcholinesterase inhibitor. All this really does is it prevents the breakdown of acetylcholine so that the acetylcholine stays around for longer, so that it can have its beneficial effects. But, just because those neurons are lost early in disease, I don’t necessarily think that that means that acetylcholine loss is the cause of Alzheimer’s disease. It just means that these neurons are more susceptible to the pathologies that happen earlier on.