Microglia are tissue macrophages of the brain and play essential roles beyond the immune cell framework from brain development to homeostasis. Recent studies in microglia revealed the cellular origin of microglia as primitive macrophages that arise in the yolk sac, and this discovery prompted the development of the differential protocol of microglia from stem cells. The stem cell-derived primitive macrophages/microglia are then cocultured with stem cell-derived neurons and neurospheres to produce a further appropriate brain model which may contribute to providing new insights into the mechanism of physiological function of microglia. We also developed human 2D-and 3D brain organoid-model containing microglia to examine the roles of microglia in neurodegenerative diseases, especially Alzheimer‘s disease, using amyloid-β oligomers, and found the neuroprotective function of microglia against amyloid-β neurotoxicity. This presentation will outline recent trends in vitro culture models of human brains. We will further discuss its significance, limitations so far, and future prospects as a microphysiological system that is expected to provide a new approach to elucidate the pathogenesis of neurodegenerative diseases and develop therapeutic strategies.