Project description
Altered lipid and immune landscapes in Alzheimer's Disease
Alzheimer’s disease (AD) poses numerous cognitive difficulties to people worldwide. Affecting increasing numbers, the need for novel treatments is urgent. AD research has primarily focused on neural functioning, since it has long been regarded as a neurodegenerative disorder. However, emerging evidence reveals a connection between AD pathogenesis and the immune system. Moreover, recent studies have highlighted the roles of lipids in regulating immune cells. In this context, the ERC-funded BRAIN project will characterise the immune and lipid landscape of AD patients. Can imbalances in bio-active lipids affect immune homeostasis and, consequently, cognition? Investigation of this hypothesis may lead to identifying new therapeutic targets for AD.
Objective
Traditionally, AD is regarded as a neurodegenerative disease and as such, the major focus has been on investigating and treating neurodegeneration and neuronal functioning. Only the last decade, it became apparent that AD pathogenesis strongly interferes with immunological processes and vice versa. Indeed, my novel findings show that the immune system in patients with early AD is already severely derailed and highlight a specific role for CD8+ T-cells. My exciting data also suggest the importance of bio-active lipids like sphingolipids and specialized pro-resolving mediators in early AD pathogenesis, possibly by controlling the immune system. The identification of how the altered lipid landscape underlies AD and affects immune homeostasis is essential to come to new insights into disease pathogenesis and to discover novel intervention strategies, the ultimate goal of the BRAIN project. I therefore here hypothesize that a misbalance in bioactive lipids plays a key role in the induction and propagation of the impaired immune homeostasis associated with AD progression, thereby forming a novel target for treatment. My key objectives are:
i) Unravel bioactive lipid signatures and define correlations with disease progression, sex, biomarkers and an unbalanced immune response in early AD,
ii) Elucidate the underlying mechanisms of uncontrolled lipid mediator balance and how this relates to the altered immune landscape,
iii) Identify key players in this process and perform proof of concept studies to define if restoring the lipid balance reinstates immune homeostasis and consequently cognition and disease pathogenesis in AD.
Together this study will provide in-depth understanding of how bio-active lipids affect immune mediated processes that underlie disease progression, investigate interaction thereof and decode underlying mechanisms to pave the way towards the development of improved prognostic/diagnostic tools and identification of novel therapeutic targets.
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
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine physiology homeostasis
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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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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.
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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.
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Call for proposal
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(opens in new window) ERC-2022-ADG
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1081 HV Amsterdam
Netherlands
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