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Project information
Uncovering molecular mechanisms of Alzheimer’s disease initiation using brain organoids (AD Brain Organoids)

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Project Identification
GA21-21510S
Project Period
1/2021 - 12/2023
Investor / Pogramme / Project type
Czech Science Foundation
  • Standard Projects
MU Faculty or unit
Faculty of Medicine

Alzheimer´s disease (AD) is an incurable progressive neurodegenerative disorder in the elderly population worldwide. However, despite tremendous effort, the initial trigger of AD initiation that likely happens decades before the AD diagnosis is still unknown. And while the current body of research supports the concept that protein aggregation initiates the onset of AD, failure of over 413 clinical trials performed thus far that aimed to treat AD highlights the importance of introducing novel analytical strategies and methods to explore this disease from a new unbiased perspective. Therefore, the overall objective of this project is to determine which molecules, molecular pathways, and cell types are altered during the initial phase of AD development and use this knowledge to validate markers (and possibly “druggable targets”) of early disease onset. Specifically, we aim to 1) perform single-cell sequencing of our established functional AD-iPSCs-based model of brain organoids in the timeline experiments; 2) use unbiased data analysis to reveal molecules, molecular pathways, and cell types that are altered during the initiation of AD pathogenesis and pinpoint the relevant AD-driver change(s); and 3) evaluate if any of these novel findings could be used as early disease onset marker or possibly as AD drug-targets and perform functional studies of selected molecules. To this date, such single-cell seq analysis of AD-brain organoids has not been performed, nor has any of the available single-cell seq research from post-mortem AD-brains addressed the initial steps leading to the manifestation of AD pathology. Thus we believe that this project could significantly contribute to solving the initial trigger that stands behind the early steps of AD pathogenesis.

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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.

Sustainable Development Goal No. 3 – Good health and well-being Sustainable Development Goal No. 5 – Gender equality

Publications

Total number of publications: 7

2024

2023

2022

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