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2017 Grants - Liu
The Role of Neuronal HSPG in the Propagation of Tau
Chia-Chen Liu, Ph.D.
Mayo Clinic Jacksonville
2017 Alzheimer’s Association Research Grant (AARG)
Do HSPG proteins contribute to the movement of abnormal tau protein throughout the brain in Alzheimer’s disease?
Tau is a protein that normally functions to support nerve cell structure and help transport nutrients. In Alzheimer’s disease, tau becomes abnormally modified and can accumulate into tau tangles in the brain, one of the hallmarks of the disease. Recently, scientists have discovered that abnormal tau can move from one nerve cell to another, suggesting this may be a mechanism by which changes associated with Alzheimer’s progress across different brain regions.
Previous studies have shown that proteins on the surface of nerve cells known as heparan sulfate proteoglycans (HSPGs) may be involved in the formation of amyloid plaques in the brain – another hallmark of Alzheimer’s disease. Preliminary data suggests that HSPGs on nerve cells also contribute to the movement of abnormal tau throughout the brain, but more research is needed to understand this process.
Chia-Chen Liu, Ph.D. and colleagues have created a new genetically-engineered Alzheimer’s-like mouse that lacks HSPGs on nerve cells in the brain. This new mouse model will allow the researchers to determine if removing HSPGs prevents abnormal tau from accumulating and spreading through the brain. The researchers will also examine if the build-up of beta-amyloid contributes to the spread of abnormal tau and if this can be blocked by removing HSPGs. The researchers will use novel imaging methods that allow them to visualize how HSPGs affect the movement and formation of plaques and tangles in the brains of living mice.
The results of this study could provide insight into the molecular mechanisms that underlie the movement of abnormal tau in the brain and how beta-amyloid affects this process. Importantly, this work could identify HSPGs as a possible target for the future development of new treatments to slow or prevent Alzheimer’s disease.