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Development of human 3D organoid model of Alzheimer's disease

Project description

Modelling sporadic Alzheimer’s disease

Reliable disease models are essential for understanding pathophysiology and translating basic research into effective therapies. However, current models of Alzheimer’s disease (AD) fail to faithfully mimic the complexity of the sporadic form of the disease. With the support of the Marie Skłodowska-Curie Actions programme, the MIND-AD project aims to build a human-relevant 3D organoid model of sporadic AD using patient-derived brain extracts. The generated model is expected to recapitulate amyloid aggregation while the incorporation of microglia will help study immune cell interactions and their role in AD pathology. The clinical relevance of the proposed model will be validated against human biopsies, paving the way for advanced AD research and drug testing.

Objective

Alzheimer’s disease (AD) is the leading cause of dementia, affecting over 50 million people worldwide. Characterized by memory loss, cognitive decline, and the formation of amyloid-β plaques and neurofibrillary tangles, AD presents a significant global health burden. Current AD models, particularly in mice, fail to accurately represent the sporadic form of human AD, limiting the translation of research into effective treatments. Human-induced pluripotent stem cells (hiPSCs) offer a promising alternative for creating in vitro models, but these often lack key features of AD pathology and immune cell interactions.
This project aims to develop a 3D organoid model for sporadic AD. We will use nanoparticles as nucleation seeds to facilitate amyloid aggregation from AD patient brain extracts, allowing a more faithful representation of AD pathology. By incorporating microglia into the model, we aim recapitulate human-specific microglial states in AD. By analyzing organoids with and without microglia, we will be able to investigate whether and how microglia contribute to initiation and progression of AD-related pathology, thus providing insights into this so far unanswered question in the field. We will compare all obtained readouts to idiopathic normal pressure hydrocephalus patient brain biopsies, that contain early AD-related pathology, thus verifying that our model is able to recapitulate features of human AD brain. This innovative approach will address the limitations of current models by integrating both neuronal and immune components, offering a more comprehensive platform for studying AD and testing potential therapies. Overall, the project has the potential to advance our understanding of AD mechanisms and contribute to the development of more effective treatments.

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

ITA-SUOMEN YLIOPISTO
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 242 116,80
Address
YLIOPISTONRANTA 8
70211 KUOPIO
Finland

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Activity type
Higher or Secondary Education Establishments
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Total cost

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