Promoting neurovascular repair to improve cognitive resilience across the lifespan

This project's goal is to enhance brain resilience by promoting vascular brain health during aging. The research team's overarching hypothesis is that many people experience cognitive decline and dementia due to pathological aging. In pathological aging, mild brain injuries that would be repairable in the young, and even in older people with resilience, lead to damaged blood vessels in the brain. Ischemic brain injury is very common, it has been found that people with resilience to ischemic brain injury can repair and maintain normal brain blood vessels, whereas those that develop dementia cannot maintain normal blood vessels near sites of injury. Here, the team will test new therapies in mice aimed at preserving normal brain blood vessel function and cognition. In parallel, they will test antibody therapy and an engineered liposome therapy to block a key detrimental interaction between immune cells and blood vessels. Human liposomes are designed to home to the injury site and deliver a protein cargo to further improve brain blood vessel health. Because therapies will need to be effective in middle age as well as old age, we will test their effects in middle aged and old mice. At the end of the project we aim to move to human studies.