A microglia-containing 3D human brain organoid for studying HSV-1-induced Alzheimer’s disease

Abstract

As a progressive neurodegenerative disorder, Alzheimer’s disease (AD) can result in significant memory loss and cognitive deterioration. Several recent studies show that herpes simplex virus type I (HSV-1) is closely related to AD pathology. Microglia, the primary immune cells in the central nervous system, are also shown to play an important role in AD. In this study, we developed a microglia-containing 3-dimensional (3D) human brain organoid from human-induced pluripotent stem cells (hiPSCs) to study the relationship between microglia and HSV-1-induced AD phenotypes. We found that microglia increased the generation of amyloid-β protein (Aβ) and neurofibrillary tangles (NFTs), contributed to neural loss, and enhanced gliosis and neuroinflammation. We also employed shRNA vectors to inhibit certain cytokines related to neuroinflammation and examined the impact on Aβ aggregation. This model can facilitate future research on the treatment of AD regarding microglia and HSV-1.