CXCR4 as a Modifier of Tau Aggregation in Alzheimer's Disease

Several lines of evidence suggest that inflammation and altered function of the cell types in the brain involved in inflammation, such as microglia, represent an early and critical driver of Alzheimer’s disease (AD). Our group has recently shown that a chemokine receptor type 4 (CXCR4) found in the cell types that mediate inflammation in the brain, such as microglia, contributes to tauopathies, such as progressive supranuclear palsy, frontotemporal dementia, corticobasal degeneration, and AD. The objective of this study is to begin to determine how CXCR4 drives AD. Together, the findings from this study will define the function of a new gene that increases risk for AD and other tauopathies and will shed light on its role in disease processes.

Changes in the cell types in the brain involved in inflammation, such as microglia, represent an early and critical driver of Alzheimer’s disease (AD). Our group has recently shown that a gene found in the cell types that control inflammation in the brain, such as microglia, contributes to tauopathies such as progressive supranuclear palsy, frontotemporal dementia, corticobasal degeneration, and AD. The objective of this study is to begin to determine how this gene drives AD. To do this, we will use functional genomics and cell biological approaches in human tissue and stem cell models, and we will target this gene in a mouse model of tauopathy to define the effects of this gene on disease course in vivo. Together, the findings from this study will define the function of a new gene that increases risk for AD and other tauopathies and will shed light on its role in disease processes.