Advances in hiPSC-Derived Brain Organoids as a Model to Study Neuroinflammation in Alzheimer's Disease.

Neuroinflammation plays a fundamental role in several neurodegenerative diseases, including Alzheimer's disease (AD), the leading cause of dementia worldwide. As the main defense response of the central nervous system (CNS), neuroinflammation can be either protective or detrimental depending on the stage of the disease. The pivotal role of neuroinflammation in AD has led to increasing investigations into neuroinflammatory mechanisms, aiming to develop AD-modifying therapies. A significant advance in the field was the emergence of the human induced pluripotent stem cell (hiPSC) model, enabling the study of patient-derived cells. Moreover, the development of hiPSC-derived brain organoids, which mimic specific aspects of the human CNS, has expanded our understanding of neuroinflammation in AD. Here, we review how AD organoid models have evolved, focusing on the integration of microglia-the brain's primary immune surveillance cells. We also summarize recent findings on how glial activation and the crosstalk between microglia and other CNS cells affect AD progression. Lastly, we address the potential of hiPSC-derived organoids as a preclinical model for screening AD drugs.