October 18, 2023

Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson's disease

Written by

featured discovery icon

Ashley Harms, Ph.D.Ashley Harms, Ph.D.Ashley Harms, Ph.D., associate professor in the department of neurology, and David Figge, M.D., Ph.D., Instructor/Fellow in the Division of Laboratory Medicine and co-first author of this study, are the latest winners of the Heersink School of Medicine's Featured Discovery. This initiative celebrates important research from Heersink faculty members.

Their study, "Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson's disease,” was recently published in Nature Communications.

The study examined that Parkinson's disease involves abnormal alpha-synuclein accumulation and inflammation. In fact, Border-associated macrophages (BAMs), not microglia, are found to be responsible for CD4+ T cell antigen presentation, changing our understanding of neuroinflammatory mechanisms in the disease.

"Our prior research suggested that migrating immune cells from the periphery into the brain was crucial in neuron degeneration. However, the mechanisms underlying cell entry and activation within the brain were poorly understood,” says Harms. “Through experiments in a Parkinson's disease rodent model and confirmed with human Parkinson's brain tissue, we identified a specific group of macrophages known as border-associated macrophages that played a pivotal role in recruiting and activating peripheral immune cells in the brain."

The Heersink communications staff sat with Drs. Harms and Figge to gain insight into this study, UAB, and the science community.

Q: What compelled you to pursue this research?


Our previous studies were heavily focused on the role of microglia in activating and recruiting peripheral immune cells in Parkinson's disease. While microglia make up the vast majority of antigen-presenting cells in the brain, a recent discovery indicated a small population of border-associated macrophages that reside at the interface of the brain and periphery. Given their localization, we were curious about how these cells may be important in mediating inflammation in the brain in the context of disease.

Q: What was your most unexpected finding?


Our most unexpected finding was that this small population of macrophages in the brain, not the large population of microglia as initially thought, was critical to the recruitment and activation of peripheral immune cells in the brain.

Q: How do you feel your research will impact the science community?


This finding expands the idea that immune cells in the brain while appearing to be very similar, can have vastly different functions given the disease circumstance.

Q: What made you come to UAB?


My passion lies in the fields of neuroscience and immunology. The research conducted at UAB in these fields has played a crucial role in shaping my successful independent career.

Q: What do you find makes the science community here unique?


I believe it strongly emphasizes collaboration within our research community. Our collaboration with Dr. David Figge, M.D., Ph.D., and our utilization of cutting-edge technologies like scRNAseq to study brain macrophages through the UAB Flow Core have been particularly rewarding.