Project information
Uncovering molecular mechanisms of Alzheimer’s disease initiation using brain organoids
(AD Brain Organoids)
- 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.
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.
Publications
Total number of publications: 8
2024
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A closed 3D printed microfluidic device for automated growth and differentiation of cerebral organoids from single-cell suspension
Biotechnology Journal, year: 2024, volume: 19, edition: 8, DOI
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Generation of the Human iPSC Line from Spontaneous Late-Onset Alzheimer's Disease Patient with ApoE3/3 Genotype and Sex-, Age-, and ApoE-Matched Healthy Control
Stem cell research, year: 2024, volume: 74, edition: February 2024, DOI
2023
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Cerebral organoids derived from patients with Alzheimer´s disease with PSEN1/2 mutations have defective tissue patterning and altered development
CELL REPORTS, year: 2023, volume: 42, edition: 11, DOI
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Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate
Molecular Neurodegeneration, year: 2023, volume: 18, edition: 1, DOI
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Glioblastoma and cerebral organoids: development and analysis of an in vitro model for glioblastoma migration
MOLECULAR ONCOLOGY, year: 2023, volume: 17, edition: 4, DOI
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MicroRNA Profiling of Self-Renewing Human Neural Stem Cells Reveals Novel Sets of Differentially Expressed microRNAs During Neural Differentiation In Vitro
Stem Cell Reviews and Reports, year: 2023, volume: 19, edition: 5, DOI
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Single Cerebral Organoid Mass Spectrometry of Cell-Specific Protein and Glycosphingolipid Traits
Analytical Chemistry, year: 2023, volume: 95, edition: 6, DOI
2022
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Human iPSC-Derived Neural Models for Studying Alzheimer’s Disease: from Neural Stem Cells to Cerebral Organoids
Stem Cell Reviews and Reports, year: 2022, volume: 18, edition: 2, DOI