Basic Science and Pathogenesis.

Background: Emerging studies have identified changes in lipid processing in Alzheimer's disease patients. However, how the various brain cell types respond to these changes is unclear. Multiple Alzheimer's disease risk genes are expressed in microglia and involved in lipid sensing and processing.

Exposure of iPSC-derived human microglia to brain substrates enables the generation and manipulation of diverse transcriptional states in vitro.

Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer's disease. These cells adopt distinct transcriptional subtypes known as states. Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells.