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Multimodal Brain Imaging – Gene Relationships in Alzheimer Disease: Risk and Res...
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'... 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 ver más
30/09/2025
181K€
Duración del proyecto: 29 meses Fecha Inicio: 2023-04-26
Fecha Fin: 2025-09-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-04-26
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
Presupuesto El presupuesto total del proyecto asciende a 181K€
Líder del proyecto
ASOCIACION INSTITUTO DE INVESTIGACION SANITAR... Investigación y desarrollo asociacion
Perfil tecnológico TRL 3-4 50K