Project information
Transformative stem cell-based model of Alzheimer’s disease and advanced analytics to study the role of membrane lipids in the pathogenesis
- Project Identification
- MUNI/G/1131/2017
- Project Period
- 3/2018 - 12/2020
- Investor / Pogramme / Project type
-
Masaryk University
- Grant Agency of Masaryk University
- INTERDISCIPLINARY - Interdisciplinary research projects
- MU Faculty or unit
-
Faculty of Science
- PharmDr. Zdeněk Spáčil, Ph.D.
- RNDr. Eliška Čechová, Ph.D.
- Mgr. Vít Dubec
- Mgr. Veronika Vidová, Ph.D.
- Other MU Faculty/Unit
- Faculty of Medicine
Alzheimer's disease is the most common cause of dementia (60-80% of cases) in elderly population worldwide. The current body of research supports the concept that protein aggregation initiates the onset of Alzheimer's disease. However, in spite of the large number of available literature and studies, a mechanism of pathogenesis and potential treatment for Alzheimer's disease remains elusive. Here we apply modern and highly specific analytical techniques to relevant in vitro models able to comprehensively capture all important aspects of the human neuropathology. Implementation of such models to study Alzheimer's disease will allow for proper hypothesis testing and will drive important findings. For that reason, general objective of proposed interdisciplinary and interfaculty project is to develop and apply state-of-the-art analytical methodology to a newly introduced cell biology model to study and potentially elucidate hypothetical mechanisms of Alzheimer’s disease pathogenesis. Specifically, we aim to develop modern analytical tools suitable to determine levels of gangliosides and proteins primarily involved in aggregation. Simultaneously, we will establish an adequate in vitro model based on cerebral organoids derived from human embryonic stem cells, suitable to test hypothetical mechanisms of Alzheimer's disease pathogenesis. Subsequently, we will apply analytical methodology to the conceptual model exploring the influence of gangliosides on the development of Alzheimer's disease pathology. Finally, we also aim to challenge the in vitro cellular model with an environmental perturbation (e.g. microorganisms) and capture the resulting pathological impacts in relation to Alzheimer’s disease. We believe that proposed combination of analytical technology with disease modeling using stem cells provides a unique opportunity to bring an urgently needed new perspective the field of Alzheimer’s disease research.
Publications
Total number of publications: 10
2024
-
High-Throughput Microbore LC-MS Lipidomics to Investigate APOE Phenotypes
Analytical chemistry, year: 2024, volume: 96, edition: 1, DOI
2023
-
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
-
Pathogenesis of Alzheimer´s disease: Involvement of the choroid plexus
Alzheimer´s & Dementia, year: 2023, volume: 19, edition: 8, DOI
-
Single Cerebral Organoid Mass Spectrometry of Cell-Specific Protein and Glycosphingolipid Traits
Analytical Chemistry, year: 2023, volume: 95, edition: 6, DOI
2022
-
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
2021
-
A comparative study of synthetic winged peptides for absolute protein quantification
Nature Scientific Reports, year: 2021, volume: 11, edition: 1, DOI
-
Generation of six human iPSC lines from patients with a familial Alzheimer's disease (n=3) and sex- and age-matched healthy controls (n=3)
Stem cell research, year: 2021, volume: 53, edition: May 2021, DOI
-
Systematic Feature Filtering in Exploratory Metabolomics: Application toward Biomarker Discovery
Analytical chemistry, year: 2021, volume: 93, edition: 26, DOI
2020
-
Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1
Stem Cell Research, year: 2020, volume: 45, edition: May 2020, DOI
2018
-
Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
STEM CELL REPORTS, year: 2018, volume: 11, edition: 4, DOI