A Human iPSC-Based Chimeric Mouse Model of Alzheimers Disease in Down Syndrome

Project Narrative: Down syndrome (DS), caused by triplication of human chromosome 21, is the single most common risk factor for Alzheimer’s disease (AD) and people with DS typically develop early-onset AD and dementia by their 60s. Here, we propose to employ a novel human microglial chimeric mouse brain model that is created by transplantation of human DS induced pluripotent stem cell-derived microglia to study the role of human microglia in AD/DS in vivo. Results from this study will help us better understand the mechanisms underlying the AD in DS and may steer AD therapeutic interventions into a new direction of aiming at preventing microglial senescence or rejuvenating microglia.