2005 Investigator-Initiated Research Grant

Acetylcholine is a messenger chemical that helps deliver nerve signals from one neuron to another. The chemical binds to specific “docking sites” on neurons called receptors. One docking site in particular, called the nicotinic acetylcholine receptor (nAChR), has been linked to Alzheimer’s disease. Studies suggest that in people with the disease, some of these receptors have been lost.

Jean-Pierre Changeux, Ph.D., and colleagues will examine people with Alzheimer’s disease to determine if they have “autoantibodies” to these nicotinic receptors in their blood. Autoantibodies are antibodies that bind to and help destroy a person’s own proteins, as opposed to foreign proteins such as those on a virus or bacteria. Autoantibodies play a role in a variety of autoimmune diseases, such as multiple sclerosis.

The researchers will determine if the levels of nicotinic receptor autoantibodies in the blood of those with Alzheimer’s may be sufficient to destroy significant numbers of receptors in the brain. They will also induce production of nAChR autoantibodies in mice and then test the animals to see if they develop any learning and memory deficits. The findings may contribute to a better understanding of disease processes and demonstrate whether measurements of nAChR autoantibodies can be used in risk assessment for or diagnosis of Alzheimer’s.