2013 Grants - Siman

Functional Assessment and Treatment of Progressive Tauopathy

Robert Siman, Ph.D.
University of Pennsylvania
Philadelphia, Pennsylvania

2013 Zenith Fellows Award

Tau is a protein that is one focus of research into the causes of Alzheimer’s disease and other neurodegenerative disorders. As part of the disease process, tau aggregates into various forms inside of cells including neurofibrillary tangles, one of the hallmarks of Alzheimer’s disease. Neurodegenerative diseases in which there is abnormal aggregation of tau are commonly referred to as tauopathies.

The first region of the brain that develops neurofibrillary tangles in Alzheimer’s disease is the entorhinal cortex and its output, the perforant path. However, the effects of this early condition are not well characterized.

Robert Siman, Ph.D., and colleagues have proposed to use molecular biology techniques to create mice that develop tauopathy in the entorhinal cortex and perforant path. The researchers will then perform recordings of electrical activity in the brain to assess how that tauopathy affects brain function. They will also use anatomical techniques to assess how the tauopathy affects the structure of the entorhinal cortex.

Finally, Dr. Siman and colleagues will evaluate a drug that stabilizes tau in its normal condition to determine if drug treatment reduces tauopathy and its detrimental effects. These studies will improve our understanding of how tauopathy causes cognitive decline, and they may help to identify a treatment strategy to prevent such decline.