Targeting Blood Vessel Excitability to Reduce Tau Pathology in Alzheimer’s Disease

Overactive neurons are thought to be a driver of Alzheimer’s disease pathology. Therefore, identifying new ways to reduce brain excitability is an important strategy for treating Alzheimer’s disease. This proposal will explore how targeting the brain’s vasculature by repurposing an FDA approved drug can dampen overactive neurons and decrease Alzheimer’s pathology.

Brain hyperexcitability is a defining feature of Alzheimer’s disease and represents a promising therapeutic target for treating this devastating disease. Our preliminary data suggests that sulfonylureas, a diabetic medication used to treat high blood sugar, can act on the vasculature to reduce brain hyperexcitability and amyloid plaque formation. Since brain hyperexcitability can also drive the development of neurofibrillary tangles, we will explore whether treatment with sulfonylureas can reduce tau pathology and preserve healthy brain function. Not only will we test a novel application for sulfonylureas in the fight against Alzheimer’s disease, but we will use cutting edge imaging techniques to assess neuronal structure and network function. Ultimately, our findings would demonstrate that therapeutics directed at neurovascular function have the ability to decrease Alzheimer’s related pathology, opening the door for new therapeutic approaches for Alzheimer’s disease.