Understanding how Human Blood-Brain Barrier Cells Drive Alzheimer's Disease
First, we will use our new vascular-capturing VINE-seq technique to comprehensively determine the cells and genes dysregulated Alzheimer's disease (AD) variants. We will then use chemical biology approaches to determine how identified AD variants dysregulate brain blood-brain barrier transport functions to compromise brain health and promote AD risk.
We will apply two of our newly developed molecular approaches in our proposal: (1) VINE-seq to efficiently isolate vascular cell types from postmortem human brain tissue; and (2) bioorthogonal proteome labeling to understand the functions of vascular Alzheimer's disease risk variants. Upon study completion, we will significantly expand our understanding of how Alzheimer's disease (AD) genetic variants dysregulate human brain vascular cells to drive AD risk. These data will enable new functional studies investigating the mechanisms by which brain barrier cells contribute to neurodegenerative disease.