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2013 Grants - Teich
A Therapeutic Approach to Synaptic Dysfunction in Alzheimer's Disease
Andrew Teich, M.D., Ph.D.
Columbia University Medical Center
New York, New York
2013 New Investigator Research Grant
Brain cells normally communicate with one another by sending and receiving chemical messages. These messages are transmitted through tiny spaces in between cells called synapses. Studies have found that in Alzheimer's disease, brain cells and synapses become damaged causing cell-to-cell communications to become hindered. These detrimental brain changes ultimately lead to losses in memory and other forms of cognition, a hallmark of Alzheimer's. However, it is not known exactly how dementia-related synaptic damage occurs.
In preliminary studies, Andrew Teich, M.D., Ph.D., and colleagues have identified a protein called ZCCHC17 that may play an important role in promoting synaptic health and memory. This protein is a transcription factor, meaning it affects cellular activity by influencing how genes are converted into proteins. When the researchers reduced ZCCHC17 expression in mice, the animals experienced impairments in long term potentiation, a cellular process involved in memory and learning. The animals also showed lower than normal abilities on cognitive tests. Dr. Teich's team then studied autopsied brain samples of people with and without Alzheimer's disease. According to the results, ZCCHC17 levels in people with Alzheimer's were lower in the hippocampus (a brain region important for learning and memory) than were ZCCHC17 levels in the hippocampus of healthy people.
For their current grant, the researchers will study the effects of increasing levels of ZCCHC17 in mice with Alzheimer's-like synaptic changes and memory loss. Using a genetically modified virus, the research team will deliver the protein into the animals' brain and will then assess whether the treatment partially restores the animals' synaptic health and cognitive abilities. Results of this work could identify ZCCHC17 as a novel target for Alzheimer's therapies.