Project description
Investigating age-related changes’ impacts on Alzheimer’s disease
Alzheimer’s disease (AD) research is limited by the lack of animal models that reflect its stages. A breakthrough involved xenografting human stem cell-derived neurons into mouse brains, where they survive and show typical AD features while surrounding mouse neurons remain unaffected. Key challenges include modelling ageing and the absence of human microglia, which are crucial for understanding genetic risk. The ERC-funded XenoAD project aims to develop a method to transplant human neurons and microglia while studying neurons from healthy centenarians to understand resilience against AD. It will identify novel drug targets and biomarkers through research on age-related changes and their effects on disease. By creating animal models for sporadic AD, the project seeks to advance therapies, including potential cell transplantation.
Objective
Understanding therapeutic opportunities in Alzheimer’s disease (AD), the most common form of progressive neurodegeneration, is limited due to lack of animal models that replicate the disease’s consecutive stages. We achieved a breakthrough by xenografting human stem cell-derived neurons into mouse brains, where they integrate and survive up to two years, developing typical AD hallmarks. Neighbouring mouse neurons remain resilient to AD, underscoring unique human neuronal features not mirrored in rodents. Significant challenges persist, particularly modelling aging, the primary and most elusive risk factor for sporadic AD. The current model also lacks human microglia, crucial carriers of genetic risk for AD. We need to measure the impact of progressive disease on neuron function, as maintaining brain function is the ultimate goal. To address these challenges, we propose a novel method of transplanting human neurons that preserve their epigenetic markers of aging, together with human microglia in double xenografts. Concurrently, we will investigate neurons from healthy aging centenarians to understand the basis of AD resilience at old age. Our research tackles critical questions: (1) How do age-associated epigenetic changes modulate disease phenotype? (2) What is the molecular basis of resilience in centenarians? (3) Do newly discovered drug targets benefit neuronal function? (4) Which blood biomarkers track the effect of experimental treatments? This study focuses on human biology, using human cells, genes, and proteins, ensuring rapid translation to clinical settings. By the project’s end, we expect to identify at least four novel drug targets and their biomarkers, validated through preclinical studies. Developing the first animal models for sporadic AD is transformative for the field, allowing to map the molecular pathways in human neurons from health to degeneration. The work will lead to new therapeutics but may also lead to cell transplantation therapies for AD.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences clinical medicine transplantation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-ADG
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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.
9052 ZWIJNAARDE - GENT
Belgium
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.