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Project information
Constructing the Developmental Atlas of Alzheimer’s Disease using Cerebral Organoids and Single-Cell Transcriptomics

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Project Identification
GA24-12028S
Project Period
1/2024 - 12/2026
Investor / Pogramme / Project type
Czech Science Foundation
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MU Faculty or unit
Faculty of Medicine

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.

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Sustainable Development Goal No. 3 – Good health and well-being Sustainable Development Goal No. 5 – Gender equality Sustainable Development Goal No. 17 – Partnerships for the goals

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