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2010 Grants - Cross
In Vivo Imaging of Axonal Transport Deficits in Alzheimer's Disease
Donna Cross, Ph.D.
University of Washington
2010 New Investigator Research Grant
Axons are long, armlike structures on nerve cells that help transport nutrients and other components around the cell. In Alzheimer's disease, however, these axons become damaged and lose their ability to transport components effectively. Reduced axonal transport inhibits the activities of nerve cells and can lead to their death.
To better understand this pathological process, research teams have tried to measure the extent to which Alzheimer's disease restricts axonal transportation. One such team, led by Donna Cross, Ph.D., has been quantifying axonal transport declines in mice engineered to develop Alzheimer-like symptoms. Their work has involved the use of a sophisticated imaging method called manganese-enhanced magnetic resonance imaging (MRI).
For the proposed grant, Dr. Cross and colleagues plan to expand their earlier work by focusing on an enzyme called glycogen synthase-kinase-3 (GSK-3). GSK-3 has been associated with the production of two Alzheimer-related molecules—beta-amyloid and abnormal tau. Dr. Cross's team believes that GSK-3 may also be involved in hindering axonal transport. The researchers will test this hypothesis by administering their Alzheimer mice with a drug that inhibits GSK-3 activity. They will then use manganese-enhanced MRI to assess 1) whether the drug produces quantifiable improvements in cellular axonal transport and 2) whether such improvements may help prevent or reduce the accumulation of beta-amyloid and abnormal tau.
The findings of this study could help clarify the role that axonal transport deficits—and GSK-3—play in the development and progression of Alzheimer pathology.