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2007 Grant - Nicolle
Muscarinic Receptor Signaling and Cognitive Impairment in Alzheimer's Disease
Michelle M. Nicolle, Ph.D.
Wake Forest University Health Sciences
Winston-Salem, North Carolina
2007 Investigator-Initiated Research Grant
One of the most devastating manifestations of Alzheimer's disease is loss of "executive function," or the ability to make conscious decisions based on previously acquired information. Loss of executive function has a major impact on people's ability to carry out normal daily activities. It is believed that in Alzheimer's, executive function may be compromised by disruption of a specific type of cell surface protein called the muscarinic receptor. It is also thought that activation of these receptors, which bind chemical messengers that facilitate cell-to-cell communication between neurons, may help prevent production of beta-amyloid, a toxic protein fragment found in the amyloid plaques that are characteristic of the disease.
Michelle Nicolle, Ph.D., and colleagues plan to test the relationship between muscarinic receptor activity, beta-amyloid production and loss of executive function. Using genetically engineered mice that overproduce beta-amyloid, the researchers will administer, over a period of four weeks, small chemicals that activate the muscarinic receptors. The researchers will then assess the animals in a learning test that depends on executive function and measure muscarinic activity and levels of beta-amyloid in the brain.
The experiments will help determine whether activation of these muscarinic receptors can help restore executive function and prevent beta-amyloid production. The work will help scientists better understand the pathological process and could lead to new therapeutic strategies.