Role of microRNAs in the regulation of tau pathology

Background One of the hallmark brain changes associated with Alzheimer’s and other dementias is tau tangles. Tau tangles form when normal tau proteins become abnormally modified and clump together. These tangles can damage nerve cells leading to impaired brain function. Even though tangles are a hallmark of Alzheimer’s disease, we do not fully understand what triggers their formation. Ismael Santa-Maria Perez, Ph.D., and colleagues believe that a contributing factor in tangle formation is a group of small molecules called microRNAs. MicroRNAs can interact with genes and can turn on and off the production of certain proteins. Dr. Santa-Maria Perez’s group predicts that under normal circumstances, the tau protein is highly regulated by microRNAs and that abnormal regulation of tau protein production may promote tangles and the brain changes associated with Alzheimer’s disease. Research Plan For their current work, the research team will study how microRNAs affect the production of tau protein in mice genetically engineered to carry the human tau gene. They will administer different types of microRNAs into the brains of the mice and measure the levels of normal tau proteins and the formation of tangles. They will also determine if the microRNAs impact brain function and memory abilities in the mice. Impact The results of these studies will provide novel information on the role microRNAs play in the formation of tangles in the brain. Most importantly these findings may lay a foundation for the development of novel therapies to prevent, slow or halt Alzheimer’s disease.