Isabelle Aubert, Ph.D.
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada

2007 Investigator-Initiated Research Grant

Neurotransmitters are chemicals secreted by neurons for the purpose of sending signals to other neurons. Neurons in the brain that use the chemical acetylcholine as their neurotransmitter are called cholinergic neurons. These cells are known to be particularly susceptible to cell death during early stages of Alzheimer’s disease. Cholinergic neurons in the brain participate in many learning and memory functions that are known to decline during progression of the disease. Some evidence suggests that replacing cholinergic neurons may improve the symptoms of Alzheimer’s disease in affected persons.

Isabella Aubert, Ph.D., and colleagues have found that a naturally occurring chemical (polysialic acid), found on the surface of developing and regenerating neurons, limits the ability of those cells to produce acetycholine. In contrast, some growth factors increase the production of acetylcholine. (Growth factors are molecules that help direct the growth and development of cells.)

The researchers have developed a way to block the effects of polysialic acid, and they plan to study whether blocking polysialic acid and using growth factors improve the production of acetylcholine by cholinergic neurons. They will use these modified cells to replace missing cholinergic cells in an animal model that shows many of the same brain abnormalities as those found in people with Alzheimer’s disease.

Dr. Aubert and colleagues will then examine whether these cholinergic neurons slow or halt the progression of behavioral and biochemical changes seen in untreated animals. These studies may lead to improved treatments for the brain degeneration seen in patients with Alzheimer’s disease.