Mapping brain connectivity changes in Alzheimer’s disease

Project Summary

Aim 1: We will use a virus-dependent method that can map connections in the brain, and more importantly, map connections that are changing during disease progression. We will use this approach to identify key brain connections that change early during AD-related disease. Aim 2: We will test if combatting the changes that we identify in Aim 1 can slow or prevent the development of AD-related behavioral changes. Therefore we will inhibit the cells that we identify in Aim 1 using a chemical-genetic method and test memory and cognitive behaviors over time during disease development. 

Little is known about how connectivity changes during AD-related disease, and even less is known what changes occur early on. We also do not know where AD-related pathogenesis begins. Our research will enable us to define these early changes and causally demonstrate their role in disease. We would like to be able to identify at-risk patients before they develop AD. Our work will mark changes in identified brain cells, providing potential biomarkers to identify at risk patients as well as targets for improved therapeutic interventions.