Objective
The recently approved drugs for Alzheimer’s disease (AD), targeting amyloid plaques removal, only mildly slow patients’ cognitive decline as neuronal loss starts decades before plaque deposition. To delay AD onset before symptoms development, prevention of neuronal death should be prioritised instead.
An early AD pathological event is intraneuronal accumulation of amyloids (intraAβ) which can cause neuronal death at the pre-plaque stage. IntraAβ is only found in specific neuronal subtypes first to be lost in AD, suggesting it might underly their selective vulnerability. Reactive microglia could contribute to intraAβ as blocking neuroinflammatory processes in early AD reduces its accumulation. Whether microglia also contribute to intraAβ+ neurons selective loss is still unknown but could suggest repurposing of already available microglia targeting drugs for early neuroprotective therapies.
I will test this hypothesis in 5xFAD mice, first confirming intraAβ accumulates in the neuronal subtypes selectively lost, as it occurs in humans. I will analyse the contribution of reactive microglia to intraAβ neurons death by pharmaceutically rescuing their reactivity and determine if intraAβ neurons-associated microglia express AD high-risk genes, which drive late AD pathology. Because AD affects women more, possibly due to their higher inflammatory response, the sex-specificity in the previous analyses will also be tested. Finally, I will establish microglia-containing human brain organoids to recapitulate this synergy in a in vitro human AD model, providing a foundation for future drug testing.
By determining the potentially detrimental interplay between microglia reactivity and intraAβ+ neurons, using both in vivo and in vitro models, my project will lay the basis of extensive future work while defining my research niche. In the long term, my results will impact development of novel neuroprotective therapies for treating AD before neuronal loss.
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.
- medical and health sciences basic medicine neurology neurodegenerative diseases dementia alzheimer
- medical and health sciences basic medicine pathology
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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.
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
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.
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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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.
10124 Torino
Italy
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.