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Research Grants 2011

To view an abstract, select an author from the vertical list on the left.

2011 Grants - Sokolow

Biochemical and Functional Analyses of the Na+/Ca2+ Exchanger (NCX) in Alzheimer's Pathology

Sophie Sokolow, Ph.D.
University of California - Los Angeles
Los Angeles, California

2011 New Investigator Research Grant

Recent evidence suggests that in early Alzheimer's disease, the transportation of calcium within cells becomes disrupted. This disruption leads to abnormally high calcium deposits in certain cellular regions. Such deposits may be associated with two Alzheimer's-related proteins, beta amyloid and tau.

Sophie Sokolow, Ph.D., and colleagues have observed that altered calcium transportation enables beta-amyloid to damage the function of synapses — the tiny channels through which brain cells communicate with one another. This observation prompted the researchers to look for a mechanism that caused calcium dysregulation at synaptic sites. They found that a variant form of sodium-calcium exchanger, called NCX1-3, existed at the synapses of people with Alzheimer's disease. The sodium-calcium exchanger is a protein that normally removes excess calcium from cells. But the researchers hypothesize that variant NCX1-3 may have lost the ability to clear calcium. Moreover, this variant may assist beta-amyloid in inducing synaptic damage.

For this study, Dr. Sokolow and colleagues will use Alzheimer's-like mice to study how NCX1-3 may promote beta-amyloid-induced toxicity. They will also assess links between beta-amyloid, calcium and the overproduction of glutamate at synapses. Glutamate is normally a helpful chemical messenger in the brain, but high levels of glutamate can cause damage to synapses and other brain cell structures. The researchers will conduct their analyses using sophisticated imaging and analytical methods. Study results could identify NCX1-3 as a novel target for preventing synaptic damage and cognitive loss in Alzheimer's disease.

Alzheimer's Association International Conference | July 16-20, 2017, London, England

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