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2013 Grants - Chakrabarty
Investigating the Role of Neuroinflammation in Tau Pathology
Paramita Chakrabarty, Ph.D.
University of Florida
2013 New Investigator Research Grant
Tau protein plays several important roles in the brain, including the maintenance of brain cell structure. This protein is normally modified by a process called phosphorylation, or the adding of phosphate molecules, which changes its function. In Alzheimer's disease, however, tau molecules become excessively phosphorylated (or hyperphosphorylated) and lose their ability to carry out normal functions. Abnormal tau also tends to accumulate into toxic neurofibrillary tangles, which likely promote Alzheimer's-related brain cell dysfunction and death.
In preliminary studies with mice engineered to exhibit Alzheimer's symptoms, Paramita Chakrabarty, Ph.D., and colleagues found they could promote toxic tau accumulation by increasing brain levels of pro-inflammatory compounds called cytokines. This finding suggests a close link between two Alzheimer's disease hallmarks—tau tangles and brain inflammation.
For their current study, Dr. Chakrabarty and colleagues will use mice with Alzheimer's-like symptoms to verify and expand their earlier work. They will test whether injecting these mice with interleukin-10, a cytokine known to prevent brain inflammation, can reduce tau-related brain changes in the mice. The researchers will then inject other mice with a compound that reduces the activity of chemokines, a particular group of inflammatory promoting cytokines. These mice will be analyzed to assess whether the loss of chemokine function moderates the production and clumping of abnormal tau. Dr. Chakrabarty's team will also test whether anti-chemokine treatment ameliorates functional problems associated with tau disease, including the loss of brain cells and declines in motor function. Overall, the results of this work could shed new light on how the processes involved in brain inflammation can lead to brain changes in Alzheimer's disease, and such findings could point towards novel disease therapies.