Hypertension, Tau, and Neurodegeneration

High blood pressure or arterial hypertension, a condition affecting 30% of the US population, has damaging effects on the brain, including increasing the risk for Alzheimer’s disease. How hypertension promotes the development of Alzheimer’s disease is not clear, but it has been attributed to damage to the blood vessels of the brain caused by the elevated blood pressure. However, treatment of hypertension, while greatly reducing the risk of cerebrovascular diseases like stroke, had a small impact on cognitive impairment, suggesting that alternative pathways are involved and new therapeutic approaches are needed. In this grant proposal, we pursue the novel idea, supported by human evidence and pilot studies, that hypertension increases Alzheimer’s disease risk by promoting the brain accumulation of the protein tau, a major culprit in Alzheimer’s disease. To this end, we will determine if the elevation of blood pressure is sufficient to induce tau accumulation in the brain of hypertensive mice. Since the immune system contributes to the damaging effects of hypertension on cognition, we will also test if immune factors play a role in the tau accumulation. Finally, we will test if interventions to suppress tau accumulation prevent the development of cognitive impairment in hypertensive mice. The results of these experiments will provide a new perspective on how hypertension leads to dementia, including Alzheimer’s disease, and may suggest new disease-modifying therapies based on reducing tau accumulation.