The proposed grant aims to investigate the primary cause of Alzheimer’s disease (AD) by studying human pluripotent stem cell-derived neural organoids. Current research on AD has identified pathways commonly found altered in AD brains, such as inflammation, lipid signaling, metabolism, protein folding, or cellular senescence. However, as these alterations are already present in AD patients’ brains, it is virtually impossible to determine if they are the cause or, rather, a consequence of AD. Recently, impaired adult hippocampal neurogenesis has emerged as an important mechanism likely contributing to AD. Interestingly, both animal models and patients’ data strongly suggest that adult hippocampal neurogenesis is severely impaired with the onset of AD. Importantly, our preliminary data also show signs of premature neurodifferentiation in the early stages of neural organoid differentiation compared to non-demented controls. It is, however, unknown what molecular players are triggering this phenotype. Thus, to describe and understand the initiation of AD, the grant proposes to use single-cell sequencing to map the very early stages of the disease. Functional experiments will then be performed to identify potential candidate molecules/molecular pathways for future AD therapy. The results of this research could significantly advance our understanding of AD pathogenesis and provide potential therapeutic targets for this devastating disease.

Sustainable Development Goals

Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.