Investigating How Immune Cells From the Brain and the Blood Contribute to Alzheimer's Disease

This project aims to characterize and understand the impact of brain-infiltrating myeloid cells on Alzheimer’s disease.

Microglia, the resident immune cells of the brain parenchyma, have been widely associated with Alzheimer’s disease. However, the contribution of their peripheral immune cell counterparts to this disease remains underexplored. Increasing evidence of myeloid cell infiltration in the brain of Alzheimer’s disease patients compels us to investigate their potential impact on the disease pathogenesis. This project will take advantage of cutting-edge humanized mouse models and spatial technologies to provide important new insights into the role of different human myeloid cell populations in Alzheimer’s disease.

The potential contribution of brain-infiltrating monocytes to Alzheimer’s disease remains an open question, largely due to the technical challenges to discern between bone marrow-derived monocytes and microglia within the brain. In addition, cell lineage-tracing studies in mice do not fully recapitulate the characteristic of these populations in humans. This proposal will use unique humanized mouse models to study human myeloid cells in the context of Alzheimer’s disease, together with cutting-edge technologies to distinguish between these populations in human brain samples.

The use of human cells and tissues in this study has the potential to generate translationally relevant findings for the clinic. Understanding the contribution and mechanisms of peripheral blood monocytes in Alzheimer’s disease may identify valuable biomarkers for the diagnosis and inform the design of cell-based therapeutic strategies.