Human microglia reduce alpha-synuclein aggregation and are neuroprotective in adult mouse brain

Microglia, brain-resident immune cells, are involved in pathophysiology of several neurodegenerative diseases, including Parkinson's disease. Given significant species-specific differences in microglia gene expression, particularly in disease-risk genes, as well as the highly reactive nature of these cells, studying human microglia in a whole brain environment is essential. Here, we established a humanized mouse model by transplanting human induced pluripotent stem cell-derived hematopoietic progenitor cells into the striatum of immunodeficient adult mice and injected human alpha-synuclein preformed fibrils to model Parkinson's disease pathology. We aimed to create a novel model of Parkinson's disease and studied the response of the human microglia and mouse cells to the preformed fibrils. Overall design: iPSC-derived human microglia transplanted to the striatum of immunodeficient mice, and mouse cells, treated with alpha-synuclein preformed fibrils or saline (vehicle), or no treatment.