Project description
Genetic associations with risk and resilience in Alzheimer's disease
Genome-wide association studies identified 98 genetic loci associated with late-onset Alzheimer's disease (LOAD). However, the relationships between genetic alterations and the neurodegeneration of the human brain remain largely unknown. An in-depth characterisation of each genetic risk locus and identification of mutations potentially conferring genetic resilience could lead to the development of effective LOAD therapeutic targets. Funded by the Marie Sklodowska-Curie Actions programme, the ADRIAN project aims to find associations of the 98 LOAD genetic risk loci, tau and amyloid-ß using PET, and MRI data of neurodegeneration, including that from genetic variants conferring disease resilience. The project analysis will be based on the imaging, genetic and functional data of 3 000 participants from the Harvard aging brain study and 35 000 participants from the UK Biobank.
Objective
The list of genes contributing to increased risk of developing Alzheimer’s Disease (AD) grows every year. To date, large case-control Genome-Wide Association Studies have found 98 genetic loci associated with late-onset Alzheimer's Disease (LOAD). However, apart from a small number of genes related to familial cases, it remains largely unknown the direct relationships between genes amyloid-β and tau misfolding protein accumulation (hallmark of AD), and neurodegeneration of the human brain. Even more striking, current knowledge of mutations potentially conferring genetic resilience is sparse. A better characterization of each genetic risk loci and identification of protective genetic variants could lead to development of effective therapeutical targets, actually unavailable for AD. The goal of this project is to characterize associations between the 98 LOAD genetic risk loci, in vivo tau and amyloid-ß PET, and MRI neurodegeneration – including an examination of potential genetic variants conferring disease resilience. Hypotheses: genetic loci will show distinct spatial patterns of tau and amyloid-ß spreading and neurodegeneration, helping us to better understand AD biological heterogeneity. I expect to find different subtypes of AD with different molecular mechanism and different therapeutical targets for each subtype. I will use PET imaging of ~3,000 participants from the Harvard Aging Brain Study, and the A4 and ADNI databases. ~35,000 participants from the UK Biobank with genetic and functional and structural MRI will also be used to study the impact of genetic loci on neurodegeneration. Importantly, as a first analysis, we will search for the effects of each risk loci and protective variants conferring resilience; secondary analyses will also explore the contributions of sex and ethnic minority factors
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Keywords
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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)
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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-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-2022-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.
48903 BARAKALDO BIZKAIA
Spain
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