The Role of the Immune System in Driving Cognitive Decline

To understand how the immune system worsens cognitive decline in aging and Alzheimer’s disease.

During aging and Alzheimer’s disease, certain inflammatory responses regulated by the immune system further exacerbate the disease and contribute to impaired cognition and memory. This study focuses on delineating the machinery necessary for immune cells to amplify damaging inflammation in the body and, ultimately, the brain. Using a novel method to target a specific immune cell mechanism, Dr. Ennerfelt and colleagues will assess how impeding its associated inflammatory pathways can curb cognitive decline and Alzheimer’s progression.

This project incorporates an innovative hypothesis to uncover mechanisms by which peripheral immune cells contribute to AD pathogenesis and cognitive aging; instead of conventional approaches that require brain-penetrant molecules, these studies may expose the therapeutic potential of targeting peripheral immune responses to counteract AD- and age-associated cognitive decline.

Recent research has outlined the difficulties of developing brain-penetrant therapies that target microglia, the brain’s resident immune cells. Therefore the peripheral immune system may offer a more effective therapeutic approach for AD. Due to TREM1 being almost exclusively expressed by peripheral immune cells, we will use this receptor as a tool to study the importance of the peripheral immune response in driving AD, and ultimately expose novel targets for disease.