Transcriptomic study of human brain organoids in Alzheimer's Disease

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by the presence ofamyloid beta plaque deposition, tau hyperphosphorylation and decline in cognition. Mechanistically, these proteostatic changes are able to induce mitochondrial calcium overload that could lead to cell death. Conventional preclinical 2D in vitro AD models do not accurately recapitulate these hallmarks. As an effort to improve AD modeling, we have established iPSC-derived brain organoids (BO) harboring the PSEN1 Delta-E9 mutation and compared them to their CRISPR-Cas9-corrected isogenic controls. Organoids were also treated with an BACE-1 Inhibitor. As an effort to build into the complexity of organoid modeling, we co-cultured these organoids with their congenic iPSC-derived microglia-like cells. We have compared PSEN1 mutants and their isogenic controls. We have treated both groups with BACE-1 inhibitor, with Ferrostatin and co-cultured with their congenic microglia. We compared brain organoids with their corresponding iPSC cultures too.