The Role of Immune Cells’ Interaction in Alzheimer’s Disease Pathology

The project aims to establish whether neuroimmune interactions have beneficial or detrimental impact on Alzheimer’s disease and their influence on immune therapies.

While microglia are in the spotlight, researchers know little about how adaptive immune cells interact with Alzheimer’s amyloid plaques. MHCII is a microglia-associated Alzheimer’s risk gene that functions to mediate interaction with T cells. The relevance of the microglia-T cell interaction in Alzheimer’s is unknown. To study the contribution of this interaction to Alzheimer’s pathology, Dr. Pasciuto and her team will use genetic models to manipulate MHC II expression in mice and test efficacy of T cell-based immunotherapy in Alzheimer’s mice lacking MHCII.

Dr. Pasciuto’s research will extend the current knowledge of how the immune system changes in Alzheimer’s disease. By uncovering these mechanisms, this study builds the basis toward more precise therapies that target the immune system to protect against the progression of Alzheimer’s. Additionally, this research will establish how the Alzheimer’s risk gene MHCII influences the development of Alzheimer’s and the response to potential immune-based treatments, offering hope for more personalized approaches to combating the disease.

Microglia are on the spotlight, but we know little on how T cells interact with the Ab plaques, the major pathological hallmark of AD. Not only the role of T cells in AD is debated, also the relevance of their interaction with Microglia is unknown. Current knowledge mostly relies on systemic depletion methods, which made it difficult to ascertain the brain specific role of T cells. The novelty of our strategy will be to specifically target the interaction between microglia and T cells, and study how this interaction contributes to pathology progression and to the response to immune therapy.

Our research will extend the current knowledge of how the immune system changes in Alzheimer’s disease. By uncovering these mechanisms, we build the basis towards more precise therapies that target the immune system to protect against the progression of Alzheimer’s.

Additionally, we will establish how the Alzheimer’s risk gene MHCII influence the development of Alzheimer’s and the response to potential immune-based treatments, offering hope for more personalized approaches to combating the Disease.