Master sites of tau phosphorylation as treatment targets for Alzheimer’s disease
Alzheimer's disease is the most common cause of dementia. Current medications provide symptomatic relief but do not alter the mechanisms underpinning it. Thus, treatments that prevent or limit Alzheimer’s disease are still a major unmet clinical need. The progression of Alzheimer’s disease correlates with the abnormal accumulation of a protein called tau. Abnormal accumulation of tau is due to the protein undergoing modification, which causes it to collect with other tau proteins and form larger, abnormal structures in the brain.
Previously, I made the discovery that a few sites on tau – referred to as Master sites, can drive modification of tau. This raises the possibility that inhibiting disease-promoting Master sites could provide a novel approach to intervene and prevent modification of tau, and thus mitigate molecular processes underlying disease. I will use animal models recapitulating Alzheimer’s disease to address the role of tau Master sites. This will include interrogation of Master sites for their function in cognitive processes and may provide the molecular basis for designing new treatment strategies and/or biomarkers for the identification and prevention of tau-related disorders. This research has the potential to provide a new novel disease-limiting treatment, which would significantly benefit individuals living with tau-mediated dementia.
At the time of award, Kristie was a Postdoctoral Fellow in Molecular Neuroscience and Dementia at Flinders Health and Medical Research Institute, Flinders University, Adelaide South Australia