Biochemistry of Alzheimer's disease

Professor Donna Wilcock explains that neurotransmitter hypotheses of Alzheimer's disease are largely unspecific. Nevertheless, glutamate, serotonin, and NPY have elicited interest.

Neurotransmitters – many have been implicated in disease, and it really depends on what paper you read. You could pick a neurotransmitter, and out there somewhere is a paper that shows that that neurotransmitter is affected. Glutamate, we know, is the major neurotransmitter involved in long-term potentiation (LTP), and it’s thought that LTP is the mechanism for formation of memory. So glutamate has really been a big for focus for Alzheimer’s [disease], for obvious reasons, that if we can maybe enhance the glutamate effect, we might enhance memory. But the problem is, if you have too much glutamate, you can actually kill the neuron, because they get overexcited, something called excitotoxicity. We have to be very careful with glutamate, and glutamate is really globally expressed through the brain; it’s one of the major transmitters in the brain, so we have to be careful with that. Another one is serotonin, but serotonin is involved in a lot of behavior (e.g. depression). We know that there are some emotional issues later on in Alzheimer’s disease, in the middle to late stage Alzheimer’s disease. So, treatment at that stage for those patients with antidepressants that would target serotonin does seem to be beneficial for the emotional aspect of the disease, more so than memory. The other neurotransmitter is something called neuropeptide Y (NPY), and this seems to be important for blood flow. If we can increase blood flow in the brain, possibly you would be providing more oxygen and more nutrients to the brain to make it healthier. But really there is no good understanding as far as, is it one population? In Parkinson’s disease, we know that it’s the dopaminergic neurons that are specifically affected. It’s a very small part of the brain, and so trying to regenerate those or put back that neurotransmitter is really a very clear goal in Parkinson’s disease, but in Alzheimer’s disease, it’s not that clear cut.