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2016 Grants - Congdon
Clarifying Clearance of Tau Pathology: Extra and/or Intracellular Mechanism
Erin Congdon, Ph.D.
New York University School of Medicine
New York, New York
2016 New Investigator Research Grant
How do novel antibodies help clear abnormal tau protein from the brain?
Tau protein’s normal function is to help transport nutrients and maintain the structure of nerve cells in the brain. In Alzheimer’s disease, however, tau can become abnormally modified and lose its ability to carry out normal activities. Abnormal tau tends to clump together into structures called neurofibrillary tangles, which can hinder nerve cell communication in the brain and may contribute to nerve cell death and memory loss in Alzheimer’s.
Many research teams have explored methods for reducing the accumulation of toxic tau protein in the brain. Some of these methods involve the use of tau antibodies, which can bind to abnormal tau and clear it from the brain. While antibody techniques have shown some success in preventing tau-related diseases in the laboratory, the exact mechanisms by which tau antibodies exert their effects are unclear.
In initial studies, Erin Congdon, Ph.D., and colleagues found that certain antibodies prevented harmful tau from accumulating in nerve cells growing in laboratory dishes. The most effective of these antibodies was able to bind to a specific region of the tau protein. Other antibodies that bound to different regions were not effective at clearing tau from the nerve cells. Such findings suggest the need for precisely targeted antibody therapies.
For their current grant, Dr. Congdon’s team will carry out more extensive studies to identify which antibodies most effectively bind to harmful tau and prevent tau-related nerve cell damage. They will also determine if these antibodies can prevent the spread of abnormal tau between nerve cells. The research team will examine the biological mechanisms underlying these therapeutic effects. For example, they will determine whether the antibodies work by blocking tau accumulation outside of cells (an “extracellular” mechanism) or by clearing tau within the cells (an “intracellular” mechanism).
The results of these studies will help advance our understanding of how abnormal tau protein contributes to nerve cell damage in Alzheimer’s disease. More importantly, this research may lead to the development of novel antibody therapies for preventing, slowing, or halting Alzheimer’ disease.