PHILADELPHIA - Robert Siman, PhD, Research Professor of Neurosurgery in the Perelman School of Medicine at the University of Pennsylvania, has received a Zenith Fellows Award from the Alzheimer's Association for his personal commitment to the advancement of Alzheimer's disease research, and his research contributions to better understanding and curing the disease.
The $450,000 award, provided over three years, will allow Dr. Siman's lab to pursue research looking at neural pathways critical in the Alzheimer's disease process, particularly to develop novel ways to model how tau protein may drive the disease progression and therapies to protect neural pathways and prevent structural and functional signs of disease.
"This award will allow us to continue exploring some less obvious drivers and impairments in Alzheimer's disease, research which may not have been funded otherwise," said Siman."For example, we're looking at how the protein tau impacts neural circuits in the perforant pathway to the hippocampus, which is important for learning and memory and is impaired early in Alzheimer's disease progression. We're also developing a new animal model of Alzheimer's disease using a viral vector to deliver human tau protein to the perforant pathway of healthy, wild-type or non-transgenic mice."
In a previous pilot study funded by Penn's Institute of Aging, Dr. Siman's team, in partnership with Penn's Vector Core team, successfully identified a viral vector particularly capable to drive expression of any foreign gene in the perforant pathway of mice. The Penn Vector Core has previously focused on treatments and therapies, such as gene therapies for congenital forms of blindness and cancer, and their expertise is now being extended into this research area. In this setting, the vector can drive production of human tau protein directly in the specific area of the brain where the disease appears to initiate.
The next step, now underway, is to use the mouse model using the viral vector to determine how structural changes caused by tau disrupt function in the perforant pathways. From there, researchers hope to develop treatments to protect these neural pathways, and prevent structural and functional signs of disease.
The Zenith Fellows Awards were initiated by the Alzheimer’s Association in 1991 to provide major support for investigators who have contributed significantly to the field of Alzheimer’s disease research or made significant contributions to other areas of science and are now focusing on Alzheimer‘s disease, and who are likely to make substantial contributions in the future.
Zenith Award-funded research must be on the “cutting edge” of basic science or biomedical research and thus may not conform to current conventional scientific wisdom or may challenge the prevailing orthodoxy. Zenith Award-funded research addresses fundamental problems related to early detection, cause, progression, treatment and/or prevention of Alzheimer‘s disease.

