Creating a model for tauopathy using brain organoids
When studying neurodegenerative disorders, a significant challenge is finding accurate, reproducible, and accessible models of the human brain. However, brain organoids – induced pluripotent stem cell (iPSC) derived, three-dimensional tissues that resemble the cellular structure of the brain – are a promising way to overcome this. In this study, forebrain organoids with a MAPT mutation were cultured as a potential model for tauopathies, which are neurodegenerative disorders associated with the formation of tau neurofibrillary tangles in neurons. This category includes both rare diseases, such as progressive supranuclear palsy (PSP), and prevalent ones, such as Alzheimer’s disease. Immunofluorescence staining revealed similar neuronal development between wild type and MAPT variant organoids, and by day 75, MAPT mutant organoids visually appeared to have more tau accumulation than wild type organoids, though these results are preliminary and need further validation. As the organoids continue to develop, we will continue analysis to test their efficacy as a disease model. Bulk and single-cell RNA sequencing will be used to study transcriptomic differences between the model organoids and we will perform ELISA to characterize p-tau expression. In the future, organoid models for tauopathy may be used to study neurodegenerative disease causes, pathology, and treatments with greater accessibility and efficiency.
