Grant: Project Grant

A major challenge limiting the development and application of therapies for brain disorders is the inaccessibility of the human brain for diagnostic biopsies. Unlike in conditions such as cancer where biopsies often guide life-changing treatments, it is often challenging to link an individual patient's brain disorder to its underlying cellular cause. Partly as a result, even disorders like major depression with effective treatments often require multiple rounds of trial and error to find fruitful drugs and dosing strategies for each patient. Our project's goal is to better understand changes in brain cells as people age into late life. In particular, we aim to discover biological factors that govern why some individuals are more likely to have dysfunction of certain types of neurons as they age. By using brain tissue collected from donors after their death, we can begin to unravel the causes of such cellular changes by comparing different groups of people, like those who have specific genetic variants or those who had a brain disorder during their lives. We will apply this knowledge to develop biomarkers that can predict a patient's degree of neuron-specific vulnerability using simple, routinely-accessible assays, like genetics and brain imaging. We will ask how increased risk for dysfunction of specific neuron types may underlie cognitive decline and other behavioral changes in late life. We ultimately aim for our approaches to deliver on the promise of personalized medicine for brain disorders by helping guide treatment decisions in the clinic.